Proteopedia - User contributions [en]

Hen Egg-White (HEW) Lysozyme

2011-04-20T18:49:39Z

Anne Goodling:

'''Introduction'''

Lysozyme - also known as muramidase, or glycoside hydrolase - is a powerful enzyme of biological significance found in abundance in tears, saliva, and human milk. In humans, it is encoded in the ''LYZ'' gene. Although it is responsible for the initial digestion of starches in the mouth, it is most widely identified as a non-specific defense in gram positive bacteria and in many species of fungi. Due to its antibacterial effects, it is a strong component of the innate immune system, and is an important part of an infant's diet to ward off diarrheal diseases. Since it is a small, easily available, and highly stable protein containing only 129 amino acid residues, it has been subject to extensive research regarding its function and structure. Hen Egg White (HEW) Lysozyme is shown below.

===History===

Lysozyme is an enzyme known for its unique ability to degrade the polysaccharide architecture of many kinds of cell walls, normally for the purpose of protection against bacterial infection<ref>Lysozyme. 2010. Citizendium.org. http://en.citizendium.org/wiki/Lysozyme</ref>. Its effects were first noticed by Laschtschenko in 1909. It was officially characterized and termed “lysozyme” by Alexander Fleming, the same person credited for the accidental discovery of penicillin.
The characterization of lysozyme in 1922 by Alexander Fleming was providential in that the undertaken experiment related to the discovery of lysozyme was not geared toward any knowledge of such a protein as lysozyme <ref>Lysozyme. 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>. During the unrelated experiment, nasal drippings were inadvertently introduced to a petri dish containing a bacterial culture, which culture consequently exhibited the results of an as yet unknown enzymatic reaction. The observation of this unknown reaction led to further research on the components of this reaction as well as to the corresponding identification of the newfound "lysozyme." Fleming's discovery was complemented by David C. Phillips' 1965 description of the three-dimensional structure of lysozyme via a 200 pm resolution model obtained from X-ray crystallography <ref>Lysozyme, 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>. Phillips' work was especially groundbreaking since Phillips had managed to successfully elucidate the structure of an enzyme via X-ray crystallography - a feat that had never before been accomplished<ref>Bugg, T. 1997. An Introduction to Enzyme and Coenzyme Chemistry. Blackwell Science Ltd., Oxford </ref>. Phillips' research also led to the first sufficiently described enzymatic mechanism of catalytic action <ref>1967. Proc R Soc Lond B Bio 167 (1009): 389–401.</ref>. Thus, Phillips' elucidation of the function of lysozyme led Phillips to reach a more general conclusion on the diversity of enzymatic chemical action in relation to enzymatic structure. Clearly, the findings of Phillips as well as the more general historical development of the understanding of the structure and function of lysozyme have been paramount to the more general realm of enzyme chemistry.

[[Image:nag-nam2.jpg|thumb|left|350px|Lysozyme Cleavage Site]]
<ref>Image from: http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/proteins/lysozyme.htm</ref>

'''Function'''

Lysozyme is known for damaging bacterial cell walls by catalyzing the hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid (NAM) and N-acetyl-D-glucosamine (NAG) residues in peptidoglycan, and between N-acetyl-D-glucosamine residues in chitodextrins. In this way, lysozyme is efficient in lysing the cell walls of both bacteria and fungi. The location of cleavage for lysozyme on this architectural theme is the β(1-4) glycosidic linkage connecting the C1 carbon of NAM to the C4 carbon of NAG.

The particular substrate of preference for this cleavage type is a (NAG-NAM)₃ hexasaccharide, within which substrate occurs the
cleaving target glycosidic bond, NAM₄-β-O-NAG₅. The individual hexasaccharide binding units are designated A-F, with NAM₄-β-O-NAG₅ glycosidic bond cleavage preference corresponding to a D-E unit glycosidic bond cleavage preference.

= Enzymatic Activity of Lysozyme =

Enzymes are designed to attract and to bind specific substrates. The active site of and lysozyme and its specific ligands are described in the following sections

==Mechanistic Features==

'''Zymogen of Lysozyme: Enzymatic Precursor'''

Zymogens are inactive enzyme precursors. Enzymes are developed in an inactive way to prevent the enzyme from digesting the cell that produced it. This process also prevents the enzyme from becoming active in the wrong portion of the body. Lysozyme's zymogen, simply titled “pre-lysozyme,” was sequenced in 1977 by R D Palmiter, J Gagnon, L H Ericsson and K A Walsh, and has since been sequenced much more extensively.

[[Image:jrip.jpg|thumb|left|350px|Mechanism of Lysozyme]]
<ref>Image from: http://www.google.com/imgres?imgurl=http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/pics-and-strucs/lysozyme-mech.gif&imgrefurl=http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/proteins/lysozyme.htm&usg=__ormapG4XKg-tR5GrMSOdSMTV4vE=&h=603&w=801&sz=7&hl=en&start=17&zoom=1&tbnid=nvr9gvFrUILDkM:&tbnh=143&tbnw=189&prev=/images%3Fq%3DThe%2Blysozyme%2Breaction%2Bmechanism%26um%3D1%26hl%3Den%26sa%3DN%26biw%3D1280%26bih%3D647%26tbs%3Disch:10%2C304&um=1&itbs=1&iact=hc&vpx=521&vpy=349&dur=448&hovh=191&hovw=254&tx=140&ty=48&ei=JQ_LTPKzLIjCsAPkzt2KDg&oei=IA_LTP74OsG78gapm-GFAQ&esq=2&page=2&ndsp=18&ved=1t:429,r:2,s:17&biw=1280&bih=647</ref>

'''Mechanism'''

The lysozyme mechanism of action results in the hydrolysis of a glycoside (hence the familial distinction of lysozyme as a glycosylase<ref>Lysozyme, 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>), which corresponds to the conversion of an acetal to a hemiacetal, which reaction (general degradation of glycosidic bond to units "capped" by newly formed hydroxyl groups) necessitates acid catalysis, since the conversion of acetal to hemiacetal involves the protonation of the reactant oxygen prior to actual bond cleavage. <ref>Pratt, C.W., Voet, D., Voet, J.G. Fundamentals of Biochemistry - Life at the Molecular Level - Third Edition. Voet, Voet and Pratt, 2008.</ref>. Furthermore, the transition state obtained from this protonation is a covalent, oxonium ion, intermediate that must obtain resonance stabilization. The need for some means of acid catalysis and covalent resonance stabilization is adequately provided by the Glu 35 and Asp 52 residues of lysozyme, respectively. The reaction mechanism of lysozyme is demonstrated below. In the following image, the reaction begins at the upper left-hand side, and proceeds according to reaction arrows.

As seen to the left, lysozyme works by hydrolyzing the glycosidic bond, distorting the bond between the NAM and NAG. This produces a glycosyl enzyme intermediate, which reacts with a water molecule to produce the product and the unchanged enzyme.

'''Active Site'''

The <scene name='Hen_Egg-White_(HEW)_Lysozyme/Act_site/2'>active site</scene> of lysozyme is formulated as a prominent cleft outlined by the two aforementioned catalytic amino acids, Glu 35 and Asp 52. The active site is geometrically bent to augment ligand binding, and the two amino acids interact with the ligand in the binding site. Asp52 is depicted in red, and Glu35 is depicted in green.

<applet load='1hew' size='350' frame='true' align='right' caption='' />

==Binding==
'''Ligands'''

A ligand is able to bind to the active site of an enzyme to form a biologically relevant complex. The model to the right shows a space-filling model of lysozyme with the protein distinguishable in brown and the ligand distinguishable in green. Another model of the ligand can be seen in this
<scene name='Hen_Egg-White_(HEW)_Lysozyme/Ligand/1'>ribbon diagram</scene>, with the ligand protruding as a space-filling model from the active site. Here, it is clear that the ligand is a polysaccharide.

The lysozyme reaction is characterized by hydrolysis of the beta (1-4) glycosidic bond between NAM and NAG. Lysozyme has a very specific active site, which can bind only six sugar rings from a polysaccharide chain. Once lysozyme binds to this chain, it hydrolyzes them. These six sugar rings represent the ligand of lysozyme. The lysozyme then distorts the fourth sugar in the six-membered complex, producing stress on the molecule and breaking the glycosidic bond.

The amino acid side-chains Glu35 and Asp52 are critical to the activity of this enzyme. Glu35 acts as a proton donor to the glycosidic bond, cleaving the C-O bond in the substrate, and Asp52 acts as a nucleophile to generate a glycosyl enzyme intermediate. The glycosyl enzyme intermediate then reacts with a water molecule to give the product of hydrolysis.

'''Inhibitors'''

Lysozyme is best inhibited by small saccharides which act competitively with the natural substrate. The smaller saccharides will bind to the first three binding sites of the cleft (sites A-C), but will not reach sites D and E, where the enzyme cuts the glycosidic bond. So, the competitive inhibitor will stick in the cleft, not allowing the substrate to bind to the enzyme complex.<ref>http://mcdb-webarchive.mcdb.ucsb.edu/sears/biochemistry/tw-enz/lysozyme/HEWL/lysozyme-overview.htm</ref> Several known inhibitors of lysozyme are: SDS, N-acetyl-D-glucosamine, and various alcohols and oxidizing agents.<ref>http://www.worthington-biochem.com/ly/default.html</ref>

<applet load='1hew' size='350' frame='true' align='left' caption='' />

= Composition and Structure of Lysozyme =

All proteins consist of carbon, hydrogen, nitrogen, oxygen, and sulfur, as do most organic molecules. Enzymes are composed in such a way as to maximize their reactivity with their desired substrate, increasing the efficiency of biological reactions. The <scene name='Sandbox_39/Elements/1'>composition of lysozyme</scene> can be seen on the left, with the carbon atoms outlined in gray, oxygen atoms in red, nitrogen atoms in blue, sulfur atoms in yellow, and the three-letter abbreviation for the <scene name='Sandbox_39/Amino_acid_residues/1'>amino acid residues</scene> in purple.

Lysozyme, like all proteins, also contains a <scene name='Sandbox_39/C_and_n_terminal_residues/1'> 3'C and 5'N terminal </scene>, and these can be seen by following the colors of the rainbow across the molecule. Starting at the red end, the 3' C terminal end, one can work the entire way through to the 5' N terminal end, showing the folding pattern and chain of the protein.

== Secondary Structure ==

Lysozyme contains five <scene name='Sandbox_38/A/2'>alpha helical</scene> regions and five regions containing <scene name='Sandbox_38/B/1'>beta sheets</scene> as displayed in this <scene name='Sandbox_38/Alphab/1'>image</scene>. Linking these secondary structures, a number of beta turns and a large number of random coils make up the remainder of the polypeptide backbone. The polypeptide backbone of lysozyme involved in the 3 antiparallel beta sheets display the beta hairpin motif of supersecondary structure. This depiction of lysozyme contains an antiparallel beta-pleated sheet, which contributes greatly to the stability of the molecule by providing the correct alignment of hydrogen bonds. Lysozyme also contains a great deal of random coil, which is seen in the white regions of the molecule.

'''Hydrogen Bonding'''

In all proteins <scene name='Sandbox_39/Hydrogen_bonds/2'>hydrogen bonds</scene> are essential for stability. In this ribbon diagram, the hydrogen bonds can be seen between the secondary structures of lysozyme highlighted in orange. Since the double bonds of the alpha carbons in the main chain of lysozyme cause torsional strain, lysozyme is limited to very specific hydrogen bonding between the amino acid residues. This representation clearly shows how crucial hydrogen bonding is to help maintain the stability of the protein.

==Amino Acid Residues==

The amino acids present in the lysozyme polypeptide sequence have a direct influence not only on primary structure, but also on the secondary and tertiary structures, which can be influenced by polarity and charge of the sidechains. The various amino acid residues
differ in their properties because of the great variety of side chains present on each amino acid. Polar and nonpolar (and charged and uncharged) side chains lead to various degrees of hydrophobicity and hydrophilicity, which affects protein folding. In lysozyme, the <scene name='Hen_Egg-White_(HEW)_Lysozyme/Residue/1'>residues</scene> that interact with substrate are displayed.

= Bonding Interactions =

'''Disulfide Bonding in Lysozyme'''

Lysozyme contains four <scene name='Sandbox_39/Disulfide_bonds/1'>disulfide bonds</scene> involving eight cysteine residues, which are highlighted in yellow on the left. Disulfide bonds are intramolecular forces that stabilize the tertiary structure of many proteins. Disulfide bonds are present in four locations in lysozyme: between Cys 6 and Cys 127, between Cys 30 and Cys 115, between Cys 64 and Cys 80 and between Cys 76 and Cys 94.

<applet load='1hew' size='350' frame='true' align='left' caption='' />

= Intermolecular Interactions =

'''Hydrophobicity'''

Lysozyme contains both hydrophobic and hydrophilic regions. ( <scene name='Hen_Egg-White_(HEW)_Lysozyme/Pink_polar_2/1'>Hydrophobicity</scene> ). The hydrophilic effect, or the desire for proteins to be at a specific position regarding water, is the single most important determinant of protein folding. These regions can be displayed with the hydrophobic regions in gray and the polar, hydrophillic regions in purple. This coloration highlights the location of these regions, showing that the majority of the hydrophobic regions are inside of the protein and that the majority of the hydrophillic regions are on the outside of the protein.

'''Polarity'''

The nature of the amino acid sidechains in the lysozyme polypeptide sequence leads to regions of varying hydrophobicities and polarities of the enzyme structure. The presence of certain regions of hydrophilicity and hydrophobicity is a driving force in determining protein structure when folding. The varying polarities of the side chains influence the locations of residues in the enzyme structure. Nonpolar residues appear blue, and polar residues appear red in the following <scene name='Sandbox_38/Non_polar_blue/1'>polarity</scene> display of lysozyme. Nonpolar residues will display hydrophobic tendencies occurring mostly on the interior of the enzyme while polar residues will increase in abundance on the surface of the protein in order to increase contact with the aqueous solvent so as to satisfy their hydrophilic nature. By observing a space-filled structural depiction of <scene name='Sandbox_38/Non_polar_blu/1'>lysozyme polarity</scene> with polar molecules colored red and nonpolar molecules colored blue the influence of polarity on nucleotide arrangement and protein folding is evident, with the blue (nonpolar) regions inside the red (polar) regions. The presence of <scene name='Hen_Egg-White_(HEW)_Lysozyme/Wuter/1'>water</scene> interacting with the various hydrophilic residues is depicted to further display how polarity affects structure. Water is depicted as yellow, and the polar and nonpolar regions remain their respective color.

'''Charge'''

Charges of the various regions of the lysozyme structure display a hydrophilic nature and thus also affect the location of that region of polypeptides and the overall folding of the protein. Charged regions of the protein will display hydrophilic tendencies and therefore will most often be located on the surface of the lysozyme molecule where they can interact with the aqueous solvent. Non-charged portions will display hydrophobic tendencies and be located on the interior of the molecule. The effect of various <scene name='Sandbox_38/Rb/1'>charges</scene> on protein structure can be visualized with charged molecules represented by red anionic and blue cationic regions, and uncharged regions colored in grey. This depiction of lysozyme uses a spacefill representation of lysozyme to depict <scene name='Sandbox_38/Chargeddd/1'>charges</scene>.

= Applications of Lysozyme =

Since lysozyme has been widely recognized for its antibacterial and antifungal properties, it has a wide variety of uses both in biochemical and pharmaceutical applications. In molecular biology, lysozyme is often used in the alkaline-lysis procedure for extracting and isolating plasmid DNA. It is used extensively in the pharmaceutical field for destroying gram-positive bacteria, and can be used to support already-existing immune defenses to fight bacterial infections. This enzyme is particularly important for preventing bacterial diseases in infants. Because of its antibacterial properties, lysozyme can also be used in the food industry to help prevent spoilage of foods.

= Discovery and Applications of Hen Egg-White Lysozyme=

<applet load='aln_1H6M_to_1HEW_2.pdb' size='300' frame='true' align='right' caption=' Hen Egg White (HEW) Lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to the active site, PDBid 1HEW' scene='User:Judy_Voet/Lysozyme/Lysozyme1/16' />
Lysozyme was the first enzyme whose X-ray structure was determined <ref> PMID 5840126</ref><ref>Phillips, D. C. The hen egg white lysozyme molecule. Proc. Natl Acad. Sci. USA 57, 483-495 (1967)</ref>. This <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>scene </scene> shows Hen Egg White (HEW) lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to a cleft in the enzyme. David Phillips, who determined the structure in 1965, saw that the cleft was large enough to fit three more saccharide units.
He therefore built a model extending the trisaccharide to a
<scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> that fits into the cleft, labeling the sugar subsites A-F<ref> coordinates of the model kindly provided by Louise Johnson</ref>. Alternately click on <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>trisaccharide</scene> and <scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> to turn the modeled portion of the hexasaccharide on and off.

The interesting thing about the model was that the only way that the hexasaccharide would fit into the cleft was if the 4th saccharide (in subsite D) was strained into a <scene name='User:Judy_Voet/Lysozyme/Half-chair/2'>half-chair conformation</scene>. This conformation is what would be necessary for the formation of an oxocarbenium ion (oxionium ion). When the model was studied, <scene name='User:Judy_Voet/Lysozyme/Glu_35/1'>Glu 35</scene> was found to be in an ideal location to act as a general acid catalyst, 3.34 Angstroms from the bridging oxygen between the 4th and 5th saccharide units. <scene name='User:Judy_Voet/Lysozyme/Asp_52/2'>Asp 52</scene> appeared to be too far away (2.69 angstroms) in the static lysozyme structure to have formed a covalent bond with C1 of the half-chair model in the D site, and no covalent intermediate had ever been detected, so Phillips proposed that it acted as an electrostatic stabilizer of the oxonium ion (referred to as The Phillips Mechanism).

<applet load='aln_1H6M_to_1HEW_2.pdb' size='200' frame='true' align='left' caption='NAG-2-deoxy-2-fluoro-glucosyl fluoride (NAG2FGlcF) bound to Glu35Gln HEW Lysozyme PDBid 1H6M' scene='User:Judy_Voet/Lysozyme/1h6m/3'/>

Then, in 2001, Stephen Withers published <scene name='User:Judy_Voet/Lysozyme/1h6m/3'>1H6M</scene>,<ref>PMID 11518970</ref> in which Glu 35 had been mutated to Gln to remove the general acid catalyst. The substrate contained NAG-2-fluoro-glucosyl fluoride (NAG2FGlcF). The fluoro group on C-1 does not require acid catalysis to be a good leaving group, and the remaining saccharide, in the absence of the acid necessary to catalyse the second step of the reaction, was demonstrated to form a <scene name='User:Judy_Voet/Lysozyme/Covalent/1'> covalent intermediate</scene>. In this <scene name='User:Judy_Voet/Lysozyme/Superposition/2'>superposition</scene> of the half chair model with 1HEW (greens) and the covalent intermediate in 1H6M (blues), note the relatively small motions of Asp 52 and C1 of the sugar ring in going from the model to the covalent intermediate. to observe the motion from the <scene name='User:Judy_Voet/Lysozyme/Asp52_halfchair/1'>half-chair</scene> to the <scene name='User:Judy_Voet/Lysozyme/Covalent/2'>covalent intermediate</scene> just toggle between the two green links.

== 3D Structures of Lysozyme ==

===Lys===

[[2x0a]], [[3iju]], [[3ijv]], [[3a8z]], [[2w1y]], [[2w1m]], [[2w1x]], [[2w1l]], [[3e3d]], [[3exd]], [[2zq3]], [[2zq4]], [[3b72]], [[3b6l]], [[2z12]], [[2z18]], [[2z19]], [[2vb1]], [[2hu3]], [[2hub]], [[2htx]], [[2hu1]], [[2yvb]], [[2epe]], [[2g4p]], [[2g4q]], [[2cgi]], [[2b5z]], [[2d4k]], [[2d91]], [[2f2n]], [[2fbb]], [[2c8o]], [[2c8p]], [[2a6u]], [[2aub]], [[2blx]], [[2bly]], [[2a7d]], [[2a7f]], [[1wtm]], [[1wtn]], [[1w6z]], [[1vdp]], [[1vdq]], [[1vds]], [[1vdt]], [[1ved]], [[1v7t]], [[1ps5]], [[2cds]], [[1lj3]], [[1lj4]], [[1lje]], [[1ljf]], [[1ljg]], [[1ljh]], [[1lji]], [[1ljj]], [[1ljk]], [[1jis]], [[1jit]], [[1jiy]], [[1jj0]], [[1jj1]], [[1jj3]], [[1iee]], [[1qio]], [[1f0w]], [[1f10]], [[1dpx]], [[1c10]], [[1qtk]], [[1lz8]], [[1lz9]], [[1bhz]], [[1bgi]], [[1bwh]], [[1bwi]], [[1bwj]], [[1bvx]], [[1hsw]], [[1hsx]], [[1lpi]], [[4lzt]], [[3lzt]], [[1aki]], [[1jpo]], [[1rfp]], [[193l]], [[194l]], [[5lym]], [[1lza]], [[3lyt]], [[4lyt]], [[5lyt]], [[6lyt]], [[2lzt]], [[1lzt]], [[1lzh]], [[2lzh]], [[7lyz]], [[1lyz]], [[2lyz]], [[3lyz]], [[4lyz]], [[5lyz]], [[6lyz]] - HEWL – chicken 
[[1xei]], [[1xej]], [[1xek]], [[1uco]], [[1lma]], [[4lym]] – HEWL low hydration 
[[1lsa]], [[1lsb]], [[1lsc]], [[1lsd]], [[1lse]], [[1lsf]], [[1lys]] – HEWL temperature influence 
[[2lym]], [[3lym]] – HEWL pressure influence 
[[132l]] – HEWL methylated 
[[1rcm]] – HEWL 3 S-S form 
[[2xbr]], [[2xbs]]- HEWL– Raman crystallography 
[[2zwb]], [[1io5]], [[1lzn]] - HEWL– Neutron 
[[1gxv]], [[1gxx]], [[1e8l]] - HEWL- NMR 
[[2hs7]], [[2hso]], [[2hs9]]- HEWL– Powder diffraction 
[[1ir7]], [[1ir8]], [[1ir9]], [[1ioq]], [[1ior]], [[1ios]], [[1iot]], [[1flq]], [[1flu]], [[1flw]], [[1fly]], [[1fn5]], [[1kxw]], [[1kxx]], [[1kxy]], [[1uia]], [[1uib]], [[1uic]], [[1uid]], [[1uie]], [[1uif]], [[1uig]], [[1uih]], [[1lsm]], [[1lsn]], [[1hel]], [[1hem]], [[1hen]], [[1heo]], [[1hep]], [[1heq]], [[1her]] – HEWL (mutant) 
[[1lyo]], [[2lyo]], [[3lyo]], [[4lyo]] – HEWL cross-linked 
[[1xft]] - tuLys – turkey - Powder diffraction 
[[1jse]], [[1tew]], [[135l]], [[2lz2]], [[1lz2]] – tuLys 
[[3lz2]] – tuLys - Laue 
[[3ab6]] – Lys + NAG3 – Hard clam 
[[2x8r]] – Lys GH25 – ''Aspergillus fumigatus'' 
[[3mgw]] – Lys G – Atlantic salmon 
[[3gxk]], [[3gxr]] – Lys G + NAG – Atlantic cod 
[[2fbd]] – HfLys 1 
[[3cb7]] – HfLys 2 
[[2zij]], [[2zik]], [[2zil]], [[2nwd]], [[1iwt]], [[1iwu]], [[1iwv]], [[1iww]], [[1iwx]], [[1iwy]], [[1iwz]], [[1jwr]], [[1jsf]], [[1rex]], [[1lz1]] – hLys – human 
[[1w08]], [[1ix0]], [[1ioc]], [[1ip1]], [[1ip2]], [[1ip3]], [[1ip4]], [[1ip5]], [[1ip6]], [[1ip7]], [[1qsw]], [[1gev]], [[1gez]], [[1gf0]], [[1gf3]], [[1gf4]], [[1gf5]], [[1gf6]], [[1gf7]], [[1i1z]], [[1i20]], [[1i22]], [[1gfr]], [[1gft]], [[1gfu]], [[1gfv]], [[1gf8]], [[1gf9]], [[1gfa]], [[1gfe]], [[1gfg]], [[1gfh]], [[1gfj]], [[1gfk]], [[1inu]], [[1gdx]], [[1ge0]], [[1ge1]], [[1ge2]], [[1ge3]], [[1ge4]], [[1gdw]], [[1gaz]], [[1gb0]], [[1gb2]], [[1gb3]], [[1gb5]], [[1gb6]], [[1gb7]], [[1gb8]], [[1gb9]], [[1gbo]], [[1gbw]], [[1gbx]], [[1gby]], [[1gbz]], [[1gay]], [[1eq4]], [[1eq5]], [[1eqe]], [[1c7p]], [[1di3]], [[1di4]], [[1di5]], [[1c43]], [[1c45]], [[1c46]], [[1ckg]], [[1cj6]], [[1cj7]], [[1cj8]], [[1cj9]], [[1ckc]], [[1ckd]], [[1ckf]], [[1ckh]], [[1b5z]], [[1b70]], [[1b7q]], [[1b7r]], [[1b7s]], [[1b7l]], [[1b7m]], [[1b7n]], [[1b7p]], [[1b5u]], [[1b5v]], [[1b5w]], [[1b5x]], [[1b5y]], [[1bb3]], [[1bb4]], [[2bqa]], [[2bqb]], [[2bqc]], [[2bqd]], [[2bqe]], [[2bqf]], [[2bqg]], [[2bqh]], [[2bqi]], [[2bqj]], [[2bqk]], [[2bql]], [[2bqm]], [[2bqn]], [[2bqo]], [[2mea]], [[2meb]], [[2mec]], [[2med]], [[2mee]], [[2mef]], [[2meg]], [[2meh]], [[2mei]], [[1wqm]], [[1wqn]], [[1wqo]], [[1wqp]], [[1wqq]], [[1wqr]], [[2heb]], [[2hea]], [[2hec]], [[2hed]], [[2hee]], [[2hef]], [[1jka]], [[1jkb]], [[1jkc]], [[1jkd]], [[1loz]], [[1lyy]], [[1oua]], [[1oub]], [[1ouc]], [[1oud]], [[1oue]], [[1ouf]], [[1oug]], [[1ouh]], [[1oui]], [[1ouj]], [[207l]], [[208l ]], [[1yam]], [[1yan]], [[1yao]], [[1yap]], [[1yaq]], [[1lmt]], [[1lhh]], [[1lhi]], [[1lhj]], [[1lhk]], [[1lhl]], [[133l]], [[134l]], [[1lz4]], [[1lz5]], [[1lz6]], [[1laa]], [[1tay]], [[1tby]], [[1tcy]], [[1tdy]], [[2lhm]], [[3lhm]] – hLys (mutant) 
[[1iy3]], [[1iy4]] – hLys - NMR 
[[2z2f]] – Lys – Bovine 
[[2cwi]], [[1el1]], [[1qqy]] – dLys - dog 
[[2z2e]] – dLys (mutant) 
[[1i56]] – dLys – NMR 
[[2dqa]] – Lys – ''Tapes japonica'' 
[[2gv0]] – Lys – Soft-shelled turtle 
[[1ivm]] – mLys M – NMR – mouse 
[[1jfx]] – Lys – ''Streptomyces coelicolor'' 
[[1gd6]] – Lys – ''Bombyx mori'' 
[[1jug]] – Lys – Echidna 
[[1dkj]] – BqLys – Bobwhite quail 
[[2ihl]] – Lys – Japanese quail 
[[1gbs]] – BsLys – Black swan 
[[1lmn]] – RtLys – Rainbow trout 
[[2eql]] – Lys – horse 
[[1ghl]] – phLys – pheasant 
[[1hhl]] – GfLys – Guinea fowl 
[[1lhm]] – Lys (mutant) – yeast 

===Lys small molecules complexes===

[[3fe0]], [[2d4i]], [[2d4j]], [[1v7s]] - HEWL+ D2O 
[[3m3u]] – HEWL Trp fluorescence 
[[2xjw]] - HEWL + CO 
[[1hf4]], [[1lks]] – HEWL + NO3 
[[3a34]], [[3ems]] - HEWL + arginine 
[[2xth]] – cLys + inhibitor K2PtBr6 
[[3a90]], [[3a91]], [[3a92]], [[3a93]], [[3a94]], [[3a95]], [[3a96]], [[3kam]], [[2pc2]], [[2bpu]], [[1t3p]], [[1h87]] – HEWL + rare earth 
[[2d6b]], [[2hg0]], [[1vat]], [[1gwd]], [[1b2k]], [[1lkr]], [[1azf]], [[8lyz]]- HEWL+ halogen 
[[1vat]] - HEWL + Xe 
[[1n4f]] - HEWL + As 
[[2i6z]] - HEWL + Pt drug 
[[2zyp]] - HEWL + poly (allyl amine) 
[[2f30]], [[2f4a]] – HEWL + urea derivative 
[[2f4g]], [[1ykx]], [[1yky]], [[1ykz]], [[1yl0]], [[1yl1]], [[1z55]] - HEWL + alcohol 
[[1dpw]] – HEWL + MPD 
[[1lcn]] – HEWL + SCN 
[[2zxs]] - HEWL with glycine-amide 
[[2h9j]], [[2h9k]], [[1yik]], [[1yil]] - HEWL + cyclam derivative 
[[1b0d]] – HEWL + p-toluene-sulfonate 
[[2q0m]] - HEWL + tricarbonylmanganese 
[[2war]] – HEWL (mutant) + chitopentaose 
[[2h5z]] – HfLys 1 + chitotetraose – House fly 
[[1hnl]] – hLys + glutathione 
[[1dkk]] – BqLys + NO3 

===Lys complex with glucoside===

[[3a3q]] – HEWL (mutant) + NAG 
[[1sf4]], [[1sf6]], [[1sf7]], [[1sfb]], [[1sfg]], [[1ja2]], [[1ja4]], [[1ja6]], [[1ja7]] – HEWL + NAG oligosaccharide – Powder diffraction 
[[1ubz]], [[1d6p]], [[1d6q]], [[1bb5]] – hLys (mutant) + glycoside 
[[1uc0]], [[1re2]], [[1rem]], [[1rey]], [[1rez]], [[1lzr]], [[1lzs]] - hLys + glycoside 
[[1ljn]], [[1jef]], [[1lzy]] – tuLys + glycoside 
[[1h6m]], [[1at5]], [[1at6]], [[1lzb]], [[1lzc]], [[1lzd]], [[1lze]], [[1lzg]], [[1hew ]]– HEWL + glycoside 
[[1lsy]], [[1lsz]] - HEWL (mutant) + glycoside 
[[1bb6]], [[1bb7]] – RtLys + glycoside 
[[1lmc]] – RtLys + bulgecin 
[[1lmo]], [[1lmp]], [[1lmq]] – RtLys + glucoside 
[[1lsp]] – BsLys + bulgecin 
[[153l]], [[154l]] – Lys +glucoside – goose 

===Phage Lys===

[[2oe4]], [[2oe7]], [[2oe9]], [[2oea]], [[1swz]], [[1cx6]], [[1qtc]], [[1qtd]], [[1qth]], [[1qsb]], [[1qs5]], [[1qs9]], [[1qtb]], [[256l]], [[206l]], [[167l]], [[168l]], [[169l]], [[170l]], [[171l]], [[172l]], [[173l]], [[174l]], [[175l]], [[176l]], [[177l]], [[178l]], [[181l]], [[182l]], [[183l]], [[184l]], [[185l]], [[186l]], [[187l]], [[188l]], [[1nhb]], [[137l]], [[216l]], [[152l]], [[149l]], [[150l]], [[151l]], [[1lyd]], [[2lzm]] - T4Lys – Enterobacteria phage T4 
[[138l]] – T4Lys cross-linked 
[[4lzm]], [[5lzm]], [[6lzm]], [[7lzm]] – T4Lys ionic strength 
[[3l2x]], [[3k2r]], [[3g3v]], [[3g3w]], [[3g3x]], [[2q9d]], [[2q9e]], [[2igc]], [[2ntg]], [[2nth]], [[2ou8]], [[2ou9]], [[1zur]], [[1zwn]], [[1zyt]], [[2cuu]], [[2a4t]] – T4Lys (mutant) spin labeled 
[[3l64]], [[3hwl]], [[3jr6]], [[3gui]], [[3c7w]], [[3c7y]], [[3c7z]], [[3c80]], [[3c81]], [[3c82]], [[3c83]], [[3c8q]], [[3c8r]], [[3c8s]], [[3cdo]], [[3cdq]], [[3cdr]], [[3cdt]], [[3cdv]], [[3f8v]], [[3f9l]], [[3fa0]], [[3fad]], [[3fi5]], [[3dke]], [[3dmv]], [[2o4w]], [[2o79]], [[2o7a]], [[2huk]], [[2hul]], [[2hum]], [[2b7x]], [[2b6t]], [[2b6w]], [[2b6x]], [[2b6y]], [[2b6z]], [[2b70]], [[2b72]], [[2b73]], [[2b74]], [[2b75]], [[1sx7]], [[1swy]], [[1sx2]], [[1t6h]], [[1ssw]], [[1ssy]], [[1t8f]], [[1t8g]], [[1t8a]], [[1t97]], [[1p56]], [[1p5c]], [[1p2l]], [[1p2r]], [[1p36]], [[1p37]], [[1p3n]], [[1p46]], [[1p64]], [[1p6y]], [[1p7s]], [[1pqd]], [[1pqi]], [[1pqj]], [[1pqk]], [[1pqm]], [[1pqo]], [[1oyu]], [[1ks3]], [[1kw5]], [[1kw7]], [[1ky0]], [[1ky1]], [[1l0j]], [[1l0k]], [[1lw9]], [[1lwg]], [[1lwk]], [[1lpy]], [[1llh]], [[1lgu]], [[1li6]], [[1jtm]], [[1jtn]], [[1jqu]], [[1kni]], [[1g06]], [[1g07]], [[1g0g]], [[1g0j]], [[1g0k]], [[1g0l]], [[1g0m]], [[1g0p]], [[1g0q]], [[1g1v]], [[1g1w]], [[1i6s]], [[257l]], [[258l]], [[260l]], [[1epy]], [[1b6i]], [[1cu6]], [[1d9w]], [[1ctw]], [[1cu0]], [[1cu2]], [[1cu3]], [[1cu5]], [[1cv1]], [[1cv4]], [[1cv5]], [[1cv6]], [[1cvk]], [[1cx7]], [[1d2w]], [[1d2y]], [[1d3f]], [[1d3j]], [[1d3m]], [[1d3n]], [[1cv3]], [[1qt3]], [[1qt4]], [[1qt5]], [[1qt6]], [[1qt7]], [[1qt8]], [[1qtv]], [[1qtz]], [[1qud]], [[1qug]], [[1quh]], [[1quo]], [[1qsq]], [[261l]], [[262l]], [[259l]], [[220l]], [[222l]], [[223l]], [[225l]], [[226l]], [[227l]], [[228l]], [[229l]], [[235l]], [[236l]], [[237l]], [[238l]], [[239l]], [[240l]], [[241l]], [[242l]], [[243l]], [[244l]], [[245l]], [[246l]], [[247l]], [[248l]], [[249l]], [[250l]], [[251l]], [[252l]], [[253l]], [[254l]], [[255l]], [[230l]], [[231l]], [[232l]], [[233l]], [[234l]], [[209l]], [[210l]], [[211l]], [[212l]], [[213l]], [[214l]], [[215l]], [[218l]], [[219l]], [[180l]], [[195l]], [[196l]], [[197l]], [[198l]], [[199l]], [[200l]], [[190l]], [[191l]], [[192l]], [[189l]], [[155l]], [[156l]], [[157l]], [[158l]], [[159l]], [[160l]], [[161l]], [[162l]], [[163l]], [[164l]], [[165l]], [[166l]], [[129l]], [[130l]], [[131l]], [[140l]], [[141l]], [[142l]], [[143l]], [[144l]], [[145l]], [[146l]], [[147l]], [[201l]], [[205l]], [[221l]], [[224l]], [[102l]], [[103l]], [[104l]], [[107l]], [[108l]], [[109l]], [[110l]], [[111l]], [[112l]], [[113l]], [[114l]], [[115l]], [[118l]], [[119l]], [[120l]], [[122l]], [[123l]], [[125l]], [[126l]], [[127l]], [[128l]], [[1dya]], [[1dyb]], [[1dyc]], [[1dyd]], [[1dye]], [[1dyf]], [[1dyg]], [[1l00]], [[1l85]], [[1l86]], [[1l87]], [[1l88]], [[1l89]], [[1l90]], [[1l91]], [[1l92]], [[1l93]], [[1l94]], [[1l95]], [[1l96]], [[1l97]], [[1l98]], [[1l99]], [[1lye]], [[1lyf]], [[1lyg]], [[1lyh]], [[1lyi]], [[1lyj]], [[217l]], [[1tla]], [[1l77]], [[1l79]], [[1l80]], [[1l81]], [[1l82]], [[2l78]], [[1l36]], [[1l37]], [[1l38]], [[1l39]], [[1l40]], [[1l41]], [[1l42]], [[1l43]], [[1l44]], [[1l45]], [[1l46]], [[1l47]], [[1l48]], [[1l49]], [[1l50]], [[1l51]], [[1l52]], [[1l53]], [[1l54]], [[1l55]], [[1l56]], [[1l57]], [[1l58]], [[1l59]], [[1l60]], [[1l61]], [[1l62]], [[1l63]], [[1l64]], [[1l65]], [[1l66]], [[1l67]], [[1l68]], [[1l69]], [[1l70]], [[1l71]], [[1l72]], [[1l73]], [[1l74]], [[1l75]], [[1l76]], [[1l17]], [[1l18]], [[1l19]], [[1l20]], [[1l21]], [[1l22]], [[1l23]], [[1l24]], [[1l25]], [[1l26]], [[1l27]], [[1l28]], [[1l29]], [[1l30]], [[1l31]], [[1l32]], [[1l33]], [[1l34]], [[1l35]], [[3lzm]], [[1l01]], [[1l02]], [[1l03]], [[1l04]], [[1l05]], [[1l06]], [[1l07]], [[1l08]], [[1l09]], [[1l10]], [[1l11]], [[1l12]], [[1l13]], [[1l14]], [[1l15]], [[1l16]] – T4Lys (mutant) 
[[1c60]], [[1c61]], [[1c62]], [[1c63]], [[1c64]], [[1c65]], [[1c66]], [[1c67]], [[1c68]], [[1c69]], [[1c6a]], [[1c6b]], [[1c6c]], [[1c6d]], [[1c6e]], [[1c6f]], [[1c6g]], [[1c6h]], [[1c6i]], [[1c6j]], [[1c6k]], [[1c6l]], [[1c6m]], [[1c6n]], [[1c6p]], [[1c6q]], [[1c6t]] - T4Lys (mutant) + noble gas 
[[3ht6]], [[3ht7]], [[3ht8]], [[3ht9]], [[3htb]], [[3hu8]], [[3huq]], [[3guj]], [[3guk]], [[3gul]], [[3gum]], [[3gun]], [[3guo]], [[3gup]], [[3dmx]], [[3dmz]], [[3dn0]], [[3dn1]], [[3dn2]], [[3dn3]], [[3dn4]], [[3dn6]], [[3dn8]], [[3dna]], [[2rb1]], [[2ray]], [[2raz]], [[2rb0]], [[2rb2]], [[2rbn]], [[2rbo]], [[2rbq]], [[2rbr]], [[2rbs]], [[2oty]],[[2otz]], [[1owy]], [[1owz]], [[1ov5]], [[1ov7]], [[1ovh]], [[1ovj]], [[1ovk]], [[1lgw]], [[1lgx]], [[1li2]], [[1li3]], [[1l83]], [[1l84]] – T4Lys (mutant) + benzene derivative 
[[3htd]], [[3htf]], [[3htg]], [[3hu9]], [[3hua]], [[3huk]], [[3hh3]], [[3hh4]], [[3hh5]], [[3hh6]], [[2rbp]], [[2ou0]], [[2f2q]], [[2f32]], [[2f47]], [[1xep]] – T4Lys (mutant) + inhibitor 
[[148l]] - T4Lys (mutant) + glucoside 
[[3d3d]], [[1d9u]] – lamLys + chitohexasaccharide 
[[1am7]] – lamLys - Enterobacteria phage λ 
[[2anv]], [[2anx]] – Lys (mutant)]] - Enterobacteria phage p22 
[[1xjt]], [[1xju]] - Lys - Enterobacteria phage p1 
[[1lba]] - T7Lys - Enterobacteria phage T7 

===Lys protein complex===

[[3m18]], [[3g3a]], [[3g3b]] - HEWL + Variable lymphocyte receptor – Marine lamprey 
[[3a67]], [[3a6b]], [[3a6c]], [[2yss]], [[2eiz]], [[2dqc]], [[2dqd]], [[2dqe]], [[2dqf]], [[2dqg]], [[2dqh]], [[2dqi]], [[2dqj]], [[1j1o]], [[1j1p]], [[1j1x]], [[1ic4]], [[1ic5]], [[1ic7]] – HEWL + mLys antibody HYHEL-10 (mutant) 
[[1xgp]], [[1xgq]], [[1xgr]], [[1xgt]], [[1xgu]] – HEWL + mLys antibody HYHEL-63 
[[3d9a]], [[2eks]], [[1ua6]], [[1c08]], [[3hfm]] – HEWL + mLys antibody HYHEL-10 
[[1uac]] - tuLys C + mLys antibody HYHEL-10 
[[1yqv]], [[2iff]] – HEWL + mLys antibody HYHEL-5 
[[1bql]] – BqLys + mLys antibody HYHEL-5 
[[1ndg]] – HEWL + mLys antibody HYHEL-8 
[[1ndm]] – HEWL + mLys antibody HYHEL-26 
[[1dqj]] - HEWL + mLys antibody HYHEL-63 
[[1nby]], [[1nbz]] – HEWL (mutant) + mLys antibody HYHEL-63 
[[1g7h]], [[1g7i]], [[1g7j]], [[1g7l]], [[1g7m]], [[1kip]], [[1kiq]], [[1kir]] – HEWL + mAnti-HEWL monoclonal antibody (mutant) 
[[1mlc]], [[1vfb]] - HEWL + mIGG1-κ D44.1 FAB 
[[1a2y]] - HEWL (mutant) + mIGG1-κ D1.3 FV 
[[1fdl]] - HEWL + mIGG1-κ D1.3 FAB 
[[1jhl]] – phLys + mIGG1-κ D11.15 FV 
[[1fbi]] – GfLys + mIGG1 F9.13.7 FAB 
[[2znw]], [[2znx]] – HEWL + hSCFV10 antibody 
[[1bvk]] - HEWL + hAnti Lys FV antibody 
[[1dzb]] – tuLys + mSCFV 1F9 
[[1zv5]], [[1zvh]], [[1zvy]], [[1zmy]], [[1ri8]], [[1rjc]], [[1xfp]], [[1jtp]], [[1jtt]], [[1jto]], [[1mel]] - HEWL + cAntibody heavy chain domain – camel 
[[1op9]] - hLys C + cAntibody heavy chain domain 
[[3otp]] – HEWL + EcProtease DO – ''Escherichia coli'' 
[[3f6z]] - HEWL + MLIC – ''Pseudomonas aeruginosa'' 
[[3eba]] – hLys C + hCABHUL6 
[[2qb0]], [[2qar]] – T4Lys/E80 TELSAM domain 
[[2i25]], [[2i26]] - HEWL +NsAntigen receptor PBLA8 variable domain – Nurse shark 
[[1sq2]], [[1t6v]] – HEWL +NsNew Antigen receptor variable domain 
[[1gpq]] – HEWL + EcInhibitor of Vertebrate Lys 
[[1aro]] – T7Lys + T7 RNA polymerase 

===Some Useful External Links===
[http://en.wikipedia.org/wiki/Lysozyme Lysozyme]

[http://en.wikipedia.org/wiki/Glycoside_hydrolase#Retaining_glycoside_hydrolases Retaining Glycoside Hydrolases]

===References===
<references/>

Hen Egg-White (HEW) Lysozyme

2011-04-20T18:44:31Z

Anne Goodling:

'''Introduction'''

Lysozyme - also known as muramidase, or glycoside hydrolase - is a powerful enzyme of biological significance found in abundance in tears, saliva, and human milk. In humans, it is encoded in the ''LYZ'' gene. Although it is responsible for the initial digestion of starches in the mouth, it is most widely identified as a non-specific defense in gram positive bacteria and in many species of fungi. Due to its antibacterial effects, it is a strong component of the innate immune system, and is an important part of an infant's diet to ward off diarrheal diseases. Since it is a small, easily available, and highly stable protein containing only 129 amino acid residues, it has been subject to extensive research regarding its function and structure. Hen Egg White (HEW) Lysozyme is shown below.

===History===

Lysozyme is an enzyme known for its unique ability to degrade the polysaccharide architecture of many kinds of cell walls, normally for the purpose of protection against bacterial infection<ref>Lysozyme. 2010. Citizendium.org. http://en.citizendium.org/wiki/Lysozyme</ref>. Its effects were first noticed by Laschtschenko in 1909. It was officially characterized and termed “lysozyme” by Alexander Fleming, the same person credited for the accidental discovery of penicillin.
The characterization of lysozyme in 1922 by Alexander Fleming was providential in that the undertaken experiment related to the discovery of lysozyme was not geared toward any knowledge of such a protein as lysozyme <ref>Lysozyme. 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>. During the unrelated experiment, nasal drippings were inadvertently introduced to a petri dish containing a bacterial culture, which culture consequently exhibited the results of an as yet unknown enzymatic reaction. The observation of this unknown reaction led to further research on the components of this reaction as well as to the corresponding identification of the newfound "lysozyme." Fleming's discovery was complemented by David C. Phillips' 1965 description of the three-dimensional structure of lysozyme via a 200 pm resolution model obtained from X-ray crystallography <ref>Lysozyme, 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>. Phillips' work was especially groundbreaking since Phillips had managed to successfully elucidate the structure of an enzyme via X-ray crystallography - a feat that had never before been accomplished<ref>Bugg, T. 1997. An Introduction to Enzyme and Coenzyme Chemistry. Blackwell Science Ltd., Oxford </ref>. Phillips' research also led to the first sufficiently described enzymatic mechanism of catalytic action <ref>1967. Proc R Soc Lond B Bio 167 (1009): 389–401.</ref>. Thus, Phillips' elucidation of the function of lysozyme led Phillips to reach a more general conclusion on the diversity of enzymatic chemical action in relation to enzymatic structure. Clearly, the findings of Phillips as well as the more general historical development of the understanding of the structure and function of lysozyme have been paramount to the more general realm of enzyme chemistry.

[[Image:nag-nam2.jpg|thumb|left|350px|Lysozyme Cleavage Site]]
<ref>Image from: http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/proteins/lysozyme.htm</ref>

'''Function'''

Lysozyme is known for damaging bacterial cell walls by catalyzing the hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid (NAM) and N-acetyl-D-glucosamine (NAG) residues in peptidoglycan, and between N-acetyl-D-glucosamine residues in chitodextrins. In this way, lysozyme is efficient in lysing the cell walls of both bacteria and fungi. The location of cleavage for lysozyme on this architectural theme is the β(1-4) glycosidic linkage connecting the C1 carbon of NAM to the C4 carbon of NAG.

The particular substrate of preference for this cleavage type is a (NAG-NAM)₃ hexasaccharide, within which substrate occurs the
cleaving target glycosidic bond, NAM₄-β-O-NAG₅. The individual hexasaccharide binding units are designated A-F, with NAM₄-β-O-NAG₅ glycosidic bond cleavage preference corresponding to a D-E unit glycosidic bond cleavage preference.

= Enzymatic Activity of Lysozyme =

Enzymes are designed to attract and to bind specific substrates. The active site of and lysozyme and its specific ligands are described in the following sections

==Mechanistic Features==

'''Zymogen of Lysozyme: Enzymatic Precursor'''

Zymogens are inactive enzyme precursors. Enzymes are developed in an inactive way to prevent the enzyme from digesting the cell that produced it. This process also prevents the enzyme from becoming active in the wrong portion of the body. Lysozyme's zymogen, simply titled “pre-lysozyme,” was sequenced in 1977 by R D Palmiter, J Gagnon, L H Ericsson and K A Walsh, and has since been sequenced much more extensively.

[[Image:jrip.jpg|thumb|left|350px|Mechanism of Lysozyme]]
<ref>Image from: http://www.google.com/imgres?imgurl=http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/pics-and-strucs/lysozyme-mech.gif&imgrefurl=http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/proteins/lysozyme.htm&usg=__ormapG4XKg-tR5GrMSOdSMTV4vE=&h=603&w=801&sz=7&hl=en&start=17&zoom=1&tbnid=nvr9gvFrUILDkM:&tbnh=143&tbnw=189&prev=/images%3Fq%3DThe%2Blysozyme%2Breaction%2Bmechanism%26um%3D1%26hl%3Den%26sa%3DN%26biw%3D1280%26bih%3D647%26tbs%3Disch:10%2C304&um=1&itbs=1&iact=hc&vpx=521&vpy=349&dur=448&hovh=191&hovw=254&tx=140&ty=48&ei=JQ_LTPKzLIjCsAPkzt2KDg&oei=IA_LTP74OsG78gapm-GFAQ&esq=2&page=2&ndsp=18&ved=1t:429,r:2,s:17&biw=1280&bih=647</ref>

'''Mechanism'''

The lysozyme mechanism of action results in the hydrolysis of a glycoside (hence the familial distinction of lysozyme as a glycosylase<ref>Lysozyme, 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>), which corresponds to the conversion of an acetal to a hemiacetal, which reaction (general degradation of glycosidic bond to units "capped" by newly formed hydroxyl groups) necessitates acid catalysis, since the conversion of acetal to hemiacetal involves the protonation of the reactant oxygen prior to actual bond cleavage. <ref>Pratt, C.W., Voet, D., Voet, J.G. Fundamentals of Biochemistry - Life at the Molecular Level - Third Edition. Voet, Voet and Pratt, 2008.</ref>. Furthermore, the transition state obtained from this protonation is a covalent, oxonium ion, intermediate that must obtain resonance stabilization. The need for some means of acid catalysis and covalent resonance stabilization is adequately provided by the Glu 35 and Asp 52 residues of lysozyme, respectively. The reaction mechanism of lysozyme is demonstrated below. In the following image, the reaction begins at the upper left-hand side, and proceeds according to reaction arrows.

As seen to the left, lysozyme works by hydrolyzing the glycosidic bond, distorting the bond between the NAM and NAG. This produces a glycosyl enzyme intermediate, which reacts with a water molecule to produce the product and the unchanged enzyme.

'''Active Site'''

The <scene name='Hen_Egg-White_(HEW)_Lysozyme/Act_site/2'>active site</scene> of lysozyme is formulated as a prominent cleft outlined by the two aforementioned catalytic amino acids, Glu 35 and Asp 52. The active site is geometrically bent to augment ligand binding, and the two amino acids interact with the ligand in the binding site. Asp52 is depicted in red, and Glu35 is depicted in green.

<applet load='1hew' size='350' frame='true' align='right' caption='' />

==Binding==
'''Ligands'''

A ligand is able to bind to the active site of an enzyme to form a biologically relevant complex. The model to the right shows a space-filling model of lysozyme with the protein distinguishable in brown and the ligand distinguishable in green. Another model of the ligand can be seen in this
<scene name='Hen_Egg-White_(HEW)_Lysozyme/Ligand/1'>ribbon diagram</scene>, with the ligand protruding as a space-filling model from the active site. Here, it is clear that the ligand is a polysaccharide.

The lysozyme reaction is characterized by hydrolysis of the beta (1-4) glycosidic bond between NAM and NAG. Lysozyme has a very specific active site, which can bind only six sugar rings from a polysaccharide chain. Once lysozyme binds to this chain, it hydrolyzes them. These six sugar rings represent the ligand of lysozyme. The lysozyme then distorts the fourth sugar in the six-membered complex, producing stress on the molecule and breaking the glycosidic bond.

The amino acid side-chains Glu35 and Asp52 are critical to the activity of this enzyme. Glu35 acts as a proton donor to the glycosidic bond, cleaving the C-O bond in the substrate, and Asp52 acts as a nucleophile to generate a glycosyl enzyme intermediate. The glycosyl enzyme intermediate then reacts with a water molecule to give the product of hydrolysis.

'''Inhibitors'''

Lysozyme is best inhibited by small saccharides which act competitively with the natural substrate. The smaller saccharides will bind to the first three binding sites of the cleft (sites A-C), but will not reach sites D and E, where the enzyme cuts the glycosidic bond. So, the competitive inhibitor will stick in the cleft, not allowing the substrate to bind to the enzyme complex.<ref>http://mcdb-webarchive.mcdb.ucsb.edu/sears/biochemistry/tw-enz/lysozyme/HEWL/lysozyme-overview.htm</ref> Several known inhibitors of lysozyme are: SDS, N-acetyl-D-glucosamine, and various alcohols and oxidizing agents.<ref>http://www.worthington-biochem.com/ly/default.html</ref>

<applet load='1hew' size='350' frame='true' align='left' caption='' />

= Composition and Structure of Lysozyme =

All proteins consist of carbon, hydrogen, nitrogen, oxygen, and sulfur, as do most organic molecules. Enzymes are composed in such a way as to maximize their reactivity with their desired substrate, increasing the efficiency of biological reactions. The <scene name='Sandbox_39/Elements/1'>composition of lysozyme</scene> can be seen on the left, with the carbon atoms outlined in gray, oxygen atoms in red, nitrogen atoms in blue, sulfur atoms in yellow, and the three-letter abbreviation for the <scene name='Sandbox_39/Amino_acid_residues/1'>amino acid residues</scene> in purple.

Lysozyme, like all proteins, also contains a <scene name='Sandbox_39/C_and_n_terminal_residues/1'> 3'C and 5'N terminal </scene>, and these can be seen by following the colors of the rainbow across the molecule. Starting at the red end, the 3' C terminal end, one can work the entire way through to the 5' N terminal end, showing the folding pattern and chain of the protein.

== Secondary Structure ==

Lysozyme contains five <scene name='Sandbox_38/A/2'>alpha helical</scene> regions and five regions containing <scene name='Sandbox_38/B/1'>beta sheets</scene> as displayed in this <scene name='Sandbox_38/Alphab/1'>image</scene>. Linking these secondary structures, a number of beta turns and a large number of random coils make up the remainder of the polypeptide backbone. The polypeptide backbone of lysozyme involved in the 3 antiparallel beta sheets display the beta hairpin motif of supersecondary structure. This depiction of lysozyme contains an antiparallel beta-pleated sheet, which contributes greatly to the stability of the molecule by providing the correct alignment of hydrogen bonds. Lysozyme also contains a great deal of random coil, which is seen in the white regions of the molecule.

'''Hydrogen Bonding'''

In all proteins <scene name='Sandbox_39/Hydrogen_bonds/2'>hydrogen bonds</scene> are essential for stability. In this ribbon diagram, the hydrogen bonds can be seen between the secondary structures of lysozyme highlighted in orange. Since the double bonds of the alpha carbons in the main chain of lysozyme cause torsional strain, lysozyme is limited to very specific hydrogen bonding between the amino acid residues. This representation clearly shows how crucial hydrogen bonding is to help maintain the stability of the protein.

==Amino Acid Residues==

The amino acids present in the lysozyme polypeptide sequence have a direct influence not only on primary structure, but also on the secondary and tertiary structures, which can be influenced by polarity and charge of the sidechains. The various amino acid residues
differ in their properties because of the great variety of side chains present on each amino acid. Polar and nonpolar (and charged and uncharged) side chains lead to various degrees of hydrophobicity and hydrophilicity, which affects protein folding. In lysozyme, the <scene name='Hen_Egg-White_(HEW)_Lysozyme/Residue/1'>residues</scene> that interact with substrate are displayed.

= Bonding Interactions =

'''Disulfide Bonding in Lysozyme'''

Lysozyme contains four <scene name='Sandbox_39/Disulfide_bonds/1'>disulfide bonds</scene> involving eight cysteine residues, which are highlighted in yellow on the left. Disulfide bonds are intramolecular forces that stabilize the tertiary structure of many proteins. Disulfide bonds are present in four locations in lysozyme: between Cys 6 and Cys 127, between Cys 30 and Cys 115, between Cys 64 and Cys 80 and between Cys 76 and Cys 94.

<applet load='1hew' size='350' frame='true' align='left' caption='' />

= Intermolecular Interactions =

'''Hydrophobicity'''

Lysozyme contains both hydrophobic and hydrophilic regions. ( <scene name='Hen_Egg-White_(HEW)_Lysozyme/Pink_polar_2/1'>Hydrophobicity</scene> ). The hydrophilic effect, or the desire for proteins to be at a specific position regarding water, is the single most important determinant of protein folding. These regions can be displayed with the hydrophobic regions in gray and the polar, hydrophillic regions in purple. This coloration highlights the location of these regions, showing that the majority of the hydrophobic regions are inside of the protein and that the majority of the hydrophillic regions are on the outside of the protein.

'''Polarity'''

The nature of the amino acid sidechains in the lysozyme polypeptide sequence leads to regions of varying hydrophobicities and polarities of the enzyme structure. The presence of certain regions of hydrophilicity and hydrophobicity is a driving force in determining protein structure when folding. The varying polarities of the side chains influence the locations of residues in the enzyme structure. Nonpolar residues appear blue, and polar residues appear red in the following <scene name='Sandbox_38/Non_polar_blue/1'>polarity</scene> display of lysozyme. Nonpolar residues will display hydrophobic tendencies occurring mostly on the interior of the enzyme while polar residues will increase in abundance on the surface of the protein in order to increase contact with the aqueous solvent so as to satisfy their hydrophilic nature. By observing a space-filled structural depiction of <scene name='Sandbox_38/Non_polar_blu/1'>lysozyme polarity</scene> with polar molecules colored red and nonpolar molecules colored blue the influence of polarity on nucleotide arrangement and protein folding is evident, with the blue (nonpolar) regions inside the red (polar) regions. The presence of <scene name='Sandbox_39/Water/1'>water</scene> interacting with the various hydrophilic residues is depicted to further display how polarity affects structure. Water is depicted as yellow, and the polar and nonpolar regions remain their respective color.

'''Charge'''

Charges of the various regions of the lysozyme structure display a hydrophilic nature and thus also affect the location of that region of polypeptides and the overall folding of the protein. Charged regions of the protein will display hydrophilic tendencies and therefore will most often be located on the surface of the lysozyme molecule where they can interact with the aqueous solvent. Non-charged portions will display hydrophobic tendencies and be located on the interior of the molecule. The effect of various <scene name='Sandbox_38/Rb/1'>charges</scene> on protein structure can be visualized with charged molecules represented by red anionic and blue cationic regions, and uncharged regions colored in grey. This depiction of lysozyme uses a spacefill representation of lysozyme to depict <scene name='Sandbox_38/Chargeddd/1'>charges</scene>.

= Applications of Lysozyme =

Since lysozyme has been widely recognized for its antibacterial and antifungal properties, it has a wide variety of uses both in biochemical and pharmaceutical applications. In molecular biology, lysozyme is often used in the alkaline-lysis procedure for extracting and isolating plasmid DNA. It is used extensively in the pharmaceutical field for destroying gram-positive bacteria, and can be used to support already-existing immune defenses to fight bacterial infections. This enzyme is particularly important for preventing bacterial diseases in infants. Because of its antibacterial properties, lysozyme can also be used in the food industry to help prevent spoilage of foods.

= Discovery and Applications of Hen Egg-White Lysozyme=

<applet load='aln_1H6M_to_1HEW_2.pdb' size='300' frame='true' align='right' caption=' Hen Egg White (HEW) Lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to the active site, PDBid 1HEW' scene='User:Judy_Voet/Lysozyme/Lysozyme1/16' />
Lysozyme was the first enzyme whose X-ray structure was determined <ref> PMID 5840126</ref><ref>Phillips, D. C. The hen egg white lysozyme molecule. Proc. Natl Acad. Sci. USA 57, 483-495 (1967)</ref>. This <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>scene </scene> shows Hen Egg White (HEW) lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to a cleft in the enzyme. David Phillips, who determined the structure in 1965, saw that the cleft was large enough to fit three more saccharide units.
He therefore built a model extending the trisaccharide to a
<scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> that fits into the cleft, labeling the sugar subsites A-F<ref> coordinates of the model kindly provided by Louise Johnson</ref>. Alternately click on <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>trisaccharide</scene> and <scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> to turn the modeled portion of the hexasaccharide on and off.

The interesting thing about the model was that the only way that the hexasaccharide would fit into the cleft was if the 4th saccharide (in subsite D) was strained into a <scene name='User:Judy_Voet/Lysozyme/Half-chair/2'>half-chair conformation</scene>. This conformation is what would be necessary for the formation of an oxocarbenium ion (oxionium ion). When the model was studied, <scene name='User:Judy_Voet/Lysozyme/Glu_35/1'>Glu 35</scene> was found to be in an ideal location to act as a general acid catalyst, 3.34 Angstroms from the bridging oxygen between the 4th and 5th saccharide units. <scene name='User:Judy_Voet/Lysozyme/Asp_52/2'>Asp 52</scene> appeared to be too far away (2.69 angstroms) in the static lysozyme structure to have formed a covalent bond with C1 of the half-chair model in the D site, and no covalent intermediate had ever been detected, so Phillips proposed that it acted as an electrostatic stabilizer of the oxonium ion (referred to as The Phillips Mechanism).

<applet load='aln_1H6M_to_1HEW_2.pdb' size='200' frame='true' align='left' caption='NAG-2-deoxy-2-fluoro-glucosyl fluoride (NAG2FGlcF) bound to Glu35Gln HEW Lysozyme PDBid 1H6M' scene='User:Judy_Voet/Lysozyme/1h6m/3'/>

Then, in 2001, Stephen Withers published <scene name='User:Judy_Voet/Lysozyme/1h6m/3'>1H6M</scene>,<ref>PMID 11518970</ref> in which Glu 35 had been mutated to Gln to remove the general acid catalyst. The substrate contained NAG-2-fluoro-glucosyl fluoride (NAG2FGlcF). The fluoro group on C-1 does not require acid catalysis to be a good leaving group, and the remaining saccharide, in the absence of the acid necessary to catalyse the second step of the reaction, was demonstrated to form a <scene name='User:Judy_Voet/Lysozyme/Covalent/1'> covalent intermediate</scene>. In this <scene name='User:Judy_Voet/Lysozyme/Superposition/2'>superposition</scene> of the half chair model with 1HEW (greens) and the covalent intermediate in 1H6M (blues), note the relatively small motions of Asp 52 and C1 of the sugar ring in going from the model to the covalent intermediate. to observe the motion from the <scene name='User:Judy_Voet/Lysozyme/Asp52_halfchair/1'>half-chair</scene> to the <scene name='User:Judy_Voet/Lysozyme/Covalent/2'>covalent intermediate</scene> just toggle between the two green links.

== 3D Structures of Lysozyme ==

===Lys===

[[2x0a]], [[3iju]], [[3ijv]], [[3a8z]], [[2w1y]], [[2w1m]], [[2w1x]], [[2w1l]], [[3e3d]], [[3exd]], [[2zq3]], [[2zq4]], [[3b72]], [[3b6l]], [[2z12]], [[2z18]], [[2z19]], [[2vb1]], [[2hu3]], [[2hub]], [[2htx]], [[2hu1]], [[2yvb]], [[2epe]], [[2g4p]], [[2g4q]], [[2cgi]], [[2b5z]], [[2d4k]], [[2d91]], [[2f2n]], [[2fbb]], [[2c8o]], [[2c8p]], [[2a6u]], [[2aub]], [[2blx]], [[2bly]], [[2a7d]], [[2a7f]], [[1wtm]], [[1wtn]], [[1w6z]], [[1vdp]], [[1vdq]], [[1vds]], [[1vdt]], [[1ved]], [[1v7t]], [[1ps5]], [[2cds]], [[1lj3]], [[1lj4]], [[1lje]], [[1ljf]], [[1ljg]], [[1ljh]], [[1lji]], [[1ljj]], [[1ljk]], [[1jis]], [[1jit]], [[1jiy]], [[1jj0]], [[1jj1]], [[1jj3]], [[1iee]], [[1qio]], [[1f0w]], [[1f10]], [[1dpx]], [[1c10]], [[1qtk]], [[1lz8]], [[1lz9]], [[1bhz]], [[1bgi]], [[1bwh]], [[1bwi]], [[1bwj]], [[1bvx]], [[1hsw]], [[1hsx]], [[1lpi]], [[4lzt]], [[3lzt]], [[1aki]], [[1jpo]], [[1rfp]], [[193l]], [[194l]], [[5lym]], [[1lza]], [[3lyt]], [[4lyt]], [[5lyt]], [[6lyt]], [[2lzt]], [[1lzt]], [[1lzh]], [[2lzh]], [[7lyz]], [[1lyz]], [[2lyz]], [[3lyz]], [[4lyz]], [[5lyz]], [[6lyz]] - HEWL – chicken 
[[1xei]], [[1xej]], [[1xek]], [[1uco]], [[1lma]], [[4lym]] – HEWL low hydration 
[[1lsa]], [[1lsb]], [[1lsc]], [[1lsd]], [[1lse]], [[1lsf]], [[1lys]] – HEWL temperature influence 
[[2lym]], [[3lym]] – HEWL pressure influence 
[[132l]] – HEWL methylated 
[[1rcm]] – HEWL 3 S-S form 
[[2xbr]], [[2xbs]]- HEWL– Raman crystallography 
[[2zwb]], [[1io5]], [[1lzn]] - HEWL– Neutron 
[[1gxv]], [[1gxx]], [[1e8l]] - HEWL- NMR 
[[2hs7]], [[2hso]], [[2hs9]]- HEWL– Powder diffraction 
[[1ir7]], [[1ir8]], [[1ir9]], [[1ioq]], [[1ior]], [[1ios]], [[1iot]], [[1flq]], [[1flu]], [[1flw]], [[1fly]], [[1fn5]], [[1kxw]], [[1kxx]], [[1kxy]], [[1uia]], [[1uib]], [[1uic]], [[1uid]], [[1uie]], [[1uif]], [[1uig]], [[1uih]], [[1lsm]], [[1lsn]], [[1hel]], [[1hem]], [[1hen]], [[1heo]], [[1hep]], [[1heq]], [[1her]] – HEWL (mutant) 
[[1lyo]], [[2lyo]], [[3lyo]], [[4lyo]] – HEWL cross-linked 
[[1xft]] - tuLys – turkey - Powder diffraction 
[[1jse]], [[1tew]], [[135l]], [[2lz2]], [[1lz2]] – tuLys 
[[3lz2]] – tuLys - Laue 
[[3ab6]] – Lys + NAG3 – Hard clam 
[[2x8r]] – Lys GH25 – ''Aspergillus fumigatus'' 
[[3mgw]] – Lys G – Atlantic salmon 
[[3gxk]], [[3gxr]] – Lys G + NAG – Atlantic cod 
[[2fbd]] – HfLys 1 
[[3cb7]] – HfLys 2 
[[2zij]], [[2zik]], [[2zil]], [[2nwd]], [[1iwt]], [[1iwu]], [[1iwv]], [[1iww]], [[1iwx]], [[1iwy]], [[1iwz]], [[1jwr]], [[1jsf]], [[1rex]], [[1lz1]] – hLys – human 
[[1w08]], [[1ix0]], [[1ioc]], [[1ip1]], [[1ip2]], [[1ip3]], [[1ip4]], [[1ip5]], [[1ip6]], [[1ip7]], [[1qsw]], [[1gev]], [[1gez]], [[1gf0]], [[1gf3]], [[1gf4]], [[1gf5]], [[1gf6]], [[1gf7]], [[1i1z]], [[1i20]], [[1i22]], [[1gfr]], [[1gft]], [[1gfu]], [[1gfv]], [[1gf8]], [[1gf9]], [[1gfa]], [[1gfe]], [[1gfg]], [[1gfh]], [[1gfj]], [[1gfk]], [[1inu]], [[1gdx]], [[1ge0]], [[1ge1]], [[1ge2]], [[1ge3]], [[1ge4]], [[1gdw]], [[1gaz]], [[1gb0]], [[1gb2]], [[1gb3]], [[1gb5]], [[1gb6]], [[1gb7]], [[1gb8]], [[1gb9]], [[1gbo]], [[1gbw]], [[1gbx]], [[1gby]], [[1gbz]], [[1gay]], [[1eq4]], [[1eq5]], [[1eqe]], [[1c7p]], [[1di3]], [[1di4]], [[1di5]], [[1c43]], [[1c45]], [[1c46]], [[1ckg]], [[1cj6]], [[1cj7]], [[1cj8]], [[1cj9]], [[1ckc]], [[1ckd]], [[1ckf]], [[1ckh]], [[1b5z]], [[1b70]], [[1b7q]], [[1b7r]], [[1b7s]], [[1b7l]], [[1b7m]], [[1b7n]], [[1b7p]], [[1b5u]], [[1b5v]], [[1b5w]], [[1b5x]], [[1b5y]], [[1bb3]], [[1bb4]], [[2bqa]], [[2bqb]], [[2bqc]], [[2bqd]], [[2bqe]], [[2bqf]], [[2bqg]], [[2bqh]], [[2bqi]], [[2bqj]], [[2bqk]], [[2bql]], [[2bqm]], [[2bqn]], [[2bqo]], [[2mea]], [[2meb]], [[2mec]], [[2med]], [[2mee]], [[2mef]], [[2meg]], [[2meh]], [[2mei]], [[1wqm]], [[1wqn]], [[1wqo]], [[1wqp]], [[1wqq]], [[1wqr]], [[2heb]], [[2hea]], [[2hec]], [[2hed]], [[2hee]], [[2hef]], [[1jka]], [[1jkb]], [[1jkc]], [[1jkd]], [[1loz]], [[1lyy]], [[1oua]], [[1oub]], [[1ouc]], [[1oud]], [[1oue]], [[1ouf]], [[1oug]], [[1ouh]], [[1oui]], [[1ouj]], [[207l]], [[208l ]], [[1yam]], [[1yan]], [[1yao]], [[1yap]], [[1yaq]], [[1lmt]], [[1lhh]], [[1lhi]], [[1lhj]], [[1lhk]], [[1lhl]], [[133l]], [[134l]], [[1lz4]], [[1lz5]], [[1lz6]], [[1laa]], [[1tay]], [[1tby]], [[1tcy]], [[1tdy]], [[2lhm]], [[3lhm]] – hLys (mutant) 
[[1iy3]], [[1iy4]] – hLys - NMR 
[[2z2f]] – Lys – Bovine 
[[2cwi]], [[1el1]], [[1qqy]] – dLys - dog 
[[2z2e]] – dLys (mutant) 
[[1i56]] – dLys – NMR 
[[2dqa]] – Lys – ''Tapes japonica'' 
[[2gv0]] – Lys – Soft-shelled turtle 
[[1ivm]] – mLys M – NMR – mouse 
[[1jfx]] – Lys – ''Streptomyces coelicolor'' 
[[1gd6]] – Lys – ''Bombyx mori'' 
[[1jug]] – Lys – Echidna 
[[1dkj]] – BqLys – Bobwhite quail 
[[2ihl]] – Lys – Japanese quail 
[[1gbs]] – BsLys – Black swan 
[[1lmn]] – RtLys – Rainbow trout 
[[2eql]] – Lys – horse 
[[1ghl]] – phLys – pheasant 
[[1hhl]] – GfLys – Guinea fowl 
[[1lhm]] – Lys (mutant) – yeast 

===Lys small molecules complexes===

[[3fe0]], [[2d4i]], [[2d4j]], [[1v7s]] - HEWL+ D2O 
[[3m3u]] – HEWL Trp fluorescence 
[[2xjw]] - HEWL + CO 
[[1hf4]], [[1lks]] – HEWL + NO3 
[[3a34]], [[3ems]] - HEWL + arginine 
[[2xth]] – cLys + inhibitor K2PtBr6 
[[3a90]], [[3a91]], [[3a92]], [[3a93]], [[3a94]], [[3a95]], [[3a96]], [[3kam]], [[2pc2]], [[2bpu]], [[1t3p]], [[1h87]] – HEWL + rare earth 
[[2d6b]], [[2hg0]], [[1vat]], [[1gwd]], [[1b2k]], [[1lkr]], [[1azf]], [[8lyz]]- HEWL+ halogen 
[[1vat]] - HEWL + Xe 
[[1n4f]] - HEWL + As 
[[2i6z]] - HEWL + Pt drug 
[[2zyp]] - HEWL + poly (allyl amine) 
[[2f30]], [[2f4a]] – HEWL + urea derivative 
[[2f4g]], [[1ykx]], [[1yky]], [[1ykz]], [[1yl0]], [[1yl1]], [[1z55]] - HEWL + alcohol 
[[1dpw]] – HEWL + MPD 
[[1lcn]] – HEWL + SCN 
[[2zxs]] - HEWL with glycine-amide 
[[2h9j]], [[2h9k]], [[1yik]], [[1yil]] - HEWL + cyclam derivative 
[[1b0d]] – HEWL + p-toluene-sulfonate 
[[2q0m]] - HEWL + tricarbonylmanganese 
[[2war]] – HEWL (mutant) + chitopentaose 
[[2h5z]] – HfLys 1 + chitotetraose – House fly 
[[1hnl]] – hLys + glutathione 
[[1dkk]] – BqLys + NO3 

===Lys complex with glucoside===

[[3a3q]] – HEWL (mutant) + NAG 
[[1sf4]], [[1sf6]], [[1sf7]], [[1sfb]], [[1sfg]], [[1ja2]], [[1ja4]], [[1ja6]], [[1ja7]] – HEWL + NAG oligosaccharide – Powder diffraction 
[[1ubz]], [[1d6p]], [[1d6q]], [[1bb5]] – hLys (mutant) + glycoside 
[[1uc0]], [[1re2]], [[1rem]], [[1rey]], [[1rez]], [[1lzr]], [[1lzs]] - hLys + glycoside 
[[1ljn]], [[1jef]], [[1lzy]] – tuLys + glycoside 
[[1h6m]], [[1at5]], [[1at6]], [[1lzb]], [[1lzc]], [[1lzd]], [[1lze]], [[1lzg]], [[1hew ]]– HEWL + glycoside 
[[1lsy]], [[1lsz]] - HEWL (mutant) + glycoside 
[[1bb6]], [[1bb7]] – RtLys + glycoside 
[[1lmc]] – RtLys + bulgecin 
[[1lmo]], [[1lmp]], [[1lmq]] – RtLys + glucoside 
[[1lsp]] – BsLys + bulgecin 
[[153l]], [[154l]] – Lys +glucoside – goose 

===Phage Lys===

[[2oe4]], [[2oe7]], [[2oe9]], [[2oea]], [[1swz]], [[1cx6]], [[1qtc]], [[1qtd]], [[1qth]], [[1qsb]], [[1qs5]], [[1qs9]], [[1qtb]], [[256l]], [[206l]], [[167l]], [[168l]], [[169l]], [[170l]], [[171l]], [[172l]], [[173l]], [[174l]], [[175l]], [[176l]], [[177l]], [[178l]], [[181l]], [[182l]], [[183l]], [[184l]], [[185l]], [[186l]], [[187l]], [[188l]], [[1nhb]], [[137l]], [[216l]], [[152l]], [[149l]], [[150l]], [[151l]], [[1lyd]], [[2lzm]] - T4Lys – Enterobacteria phage T4 
[[138l]] – T4Lys cross-linked 
[[4lzm]], [[5lzm]], [[6lzm]], [[7lzm]] – T4Lys ionic strength 
[[3l2x]], [[3k2r]], [[3g3v]], [[3g3w]], [[3g3x]], [[2q9d]], [[2q9e]], [[2igc]], [[2ntg]], [[2nth]], [[2ou8]], [[2ou9]], [[1zur]], [[1zwn]], [[1zyt]], [[2cuu]], [[2a4t]] – T4Lys (mutant) spin labeled 
[[3l64]], [[3hwl]], [[3jr6]], [[3gui]], [[3c7w]], [[3c7y]], [[3c7z]], [[3c80]], [[3c81]], [[3c82]], [[3c83]], [[3c8q]], [[3c8r]], [[3c8s]], [[3cdo]], [[3cdq]], [[3cdr]], [[3cdt]], [[3cdv]], [[3f8v]], [[3f9l]], [[3fa0]], [[3fad]], [[3fi5]], [[3dke]], [[3dmv]], [[2o4w]], [[2o79]], [[2o7a]], [[2huk]], [[2hul]], [[2hum]], [[2b7x]], [[2b6t]], [[2b6w]], [[2b6x]], [[2b6y]], [[2b6z]], [[2b70]], [[2b72]], [[2b73]], [[2b74]], [[2b75]], [[1sx7]], [[1swy]], [[1sx2]], [[1t6h]], [[1ssw]], [[1ssy]], [[1t8f]], [[1t8g]], [[1t8a]], [[1t97]], [[1p56]], [[1p5c]], [[1p2l]], [[1p2r]], [[1p36]], [[1p37]], [[1p3n]], [[1p46]], [[1p64]], [[1p6y]], [[1p7s]], [[1pqd]], [[1pqi]], [[1pqj]], [[1pqk]], [[1pqm]], [[1pqo]], [[1oyu]], [[1ks3]], [[1kw5]], [[1kw7]], [[1ky0]], [[1ky1]], [[1l0j]], [[1l0k]], [[1lw9]], [[1lwg]], [[1lwk]], [[1lpy]], [[1llh]], [[1lgu]], [[1li6]], [[1jtm]], [[1jtn]], [[1jqu]], [[1kni]], [[1g06]], [[1g07]], [[1g0g]], [[1g0j]], [[1g0k]], [[1g0l]], [[1g0m]], [[1g0p]], [[1g0q]], [[1g1v]], [[1g1w]], [[1i6s]], [[257l]], [[258l]], [[260l]], [[1epy]], [[1b6i]], [[1cu6]], [[1d9w]], [[1ctw]], [[1cu0]], [[1cu2]], [[1cu3]], [[1cu5]], [[1cv1]], [[1cv4]], [[1cv5]], [[1cv6]], [[1cvk]], [[1cx7]], [[1d2w]], [[1d2y]], [[1d3f]], [[1d3j]], [[1d3m]], [[1d3n]], [[1cv3]], [[1qt3]], [[1qt4]], [[1qt5]], [[1qt6]], [[1qt7]], [[1qt8]], [[1qtv]], [[1qtz]], [[1qud]], [[1qug]], [[1quh]], [[1quo]], [[1qsq]], [[261l]], [[262l]], [[259l]], [[220l]], [[222l]], [[223l]], [[225l]], [[226l]], [[227l]], [[228l]], [[229l]], [[235l]], [[236l]], [[237l]], [[238l]], [[239l]], [[240l]], [[241l]], [[242l]], [[243l]], [[244l]], [[245l]], [[246l]], [[247l]], [[248l]], [[249l]], [[250l]], [[251l]], [[252l]], [[253l]], [[254l]], [[255l]], [[230l]], [[231l]], [[232l]], [[233l]], [[234l]], [[209l]], [[210l]], [[211l]], [[212l]], [[213l]], [[214l]], [[215l]], [[218l]], [[219l]], [[180l]], [[195l]], [[196l]], [[197l]], [[198l]], [[199l]], [[200l]], [[190l]], [[191l]], [[192l]], [[189l]], [[155l]], [[156l]], [[157l]], [[158l]], [[159l]], [[160l]], [[161l]], [[162l]], [[163l]], [[164l]], [[165l]], [[166l]], [[129l]], [[130l]], [[131l]], [[140l]], [[141l]], [[142l]], [[143l]], [[144l]], [[145l]], [[146l]], [[147l]], [[201l]], [[205l]], [[221l]], [[224l]], [[102l]], [[103l]], [[104l]], [[107l]], [[108l]], [[109l]], [[110l]], [[111l]], [[112l]], [[113l]], [[114l]], [[115l]], [[118l]], [[119l]], [[120l]], [[122l]], [[123l]], [[125l]], [[126l]], [[127l]], [[128l]], [[1dya]], [[1dyb]], [[1dyc]], [[1dyd]], [[1dye]], [[1dyf]], [[1dyg]], [[1l00]], [[1l85]], [[1l86]], [[1l87]], [[1l88]], [[1l89]], [[1l90]], [[1l91]], [[1l92]], [[1l93]], [[1l94]], [[1l95]], [[1l96]], [[1l97]], [[1l98]], [[1l99]], [[1lye]], [[1lyf]], [[1lyg]], [[1lyh]], [[1lyi]], [[1lyj]], [[217l]], [[1tla]], [[1l77]], [[1l79]], [[1l80]], [[1l81]], [[1l82]], [[2l78]], [[1l36]], [[1l37]], [[1l38]], [[1l39]], [[1l40]], [[1l41]], [[1l42]], [[1l43]], [[1l44]], [[1l45]], [[1l46]], [[1l47]], [[1l48]], [[1l49]], [[1l50]], [[1l51]], [[1l52]], [[1l53]], [[1l54]], [[1l55]], [[1l56]], [[1l57]], [[1l58]], [[1l59]], [[1l60]], [[1l61]], [[1l62]], [[1l63]], [[1l64]], [[1l65]], [[1l66]], [[1l67]], [[1l68]], [[1l69]], [[1l70]], [[1l71]], [[1l72]], [[1l73]], [[1l74]], [[1l75]], [[1l76]], [[1l17]], [[1l18]], [[1l19]], [[1l20]], [[1l21]], [[1l22]], [[1l23]], [[1l24]], [[1l25]], [[1l26]], [[1l27]], [[1l28]], [[1l29]], [[1l30]], [[1l31]], [[1l32]], [[1l33]], [[1l34]], [[1l35]], [[3lzm]], [[1l01]], [[1l02]], [[1l03]], [[1l04]], [[1l05]], [[1l06]], [[1l07]], [[1l08]], [[1l09]], [[1l10]], [[1l11]], [[1l12]], [[1l13]], [[1l14]], [[1l15]], [[1l16]] – T4Lys (mutant) 
[[1c60]], [[1c61]], [[1c62]], [[1c63]], [[1c64]], [[1c65]], [[1c66]], [[1c67]], [[1c68]], [[1c69]], [[1c6a]], [[1c6b]], [[1c6c]], [[1c6d]], [[1c6e]], [[1c6f]], [[1c6g]], [[1c6h]], [[1c6i]], [[1c6j]], [[1c6k]], [[1c6l]], [[1c6m]], [[1c6n]], [[1c6p]], [[1c6q]], [[1c6t]] - T4Lys (mutant) + noble gas 
[[3ht6]], [[3ht7]], [[3ht8]], [[3ht9]], [[3htb]], [[3hu8]], [[3huq]], [[3guj]], [[3guk]], [[3gul]], [[3gum]], [[3gun]], [[3guo]], [[3gup]], [[3dmx]], [[3dmz]], [[3dn0]], [[3dn1]], [[3dn2]], [[3dn3]], [[3dn4]], [[3dn6]], [[3dn8]], [[3dna]], [[2rb1]], [[2ray]], [[2raz]], [[2rb0]], [[2rb2]], [[2rbn]], [[2rbo]], [[2rbq]], [[2rbr]], [[2rbs]], [[2oty]],[[2otz]], [[1owy]], [[1owz]], [[1ov5]], [[1ov7]], [[1ovh]], [[1ovj]], [[1ovk]], [[1lgw]], [[1lgx]], [[1li2]], [[1li3]], [[1l83]], [[1l84]] – T4Lys (mutant) + benzene derivative 
[[3htd]], [[3htf]], [[3htg]], [[3hu9]], [[3hua]], [[3huk]], [[3hh3]], [[3hh4]], [[3hh5]], [[3hh6]], [[2rbp]], [[2ou0]], [[2f2q]], [[2f32]], [[2f47]], [[1xep]] – T4Lys (mutant) + inhibitor 
[[148l]] - T4Lys (mutant) + glucoside 
[[3d3d]], [[1d9u]] – lamLys + chitohexasaccharide 
[[1am7]] – lamLys - Enterobacteria phage λ 
[[2anv]], [[2anx]] – Lys (mutant)]] - Enterobacteria phage p22 
[[1xjt]], [[1xju]] - Lys - Enterobacteria phage p1 
[[1lba]] - T7Lys - Enterobacteria phage T7 

===Lys protein complex===

[[3m18]], [[3g3a]], [[3g3b]] - HEWL + Variable lymphocyte receptor – Marine lamprey 
[[3a67]], [[3a6b]], [[3a6c]], [[2yss]], [[2eiz]], [[2dqc]], [[2dqd]], [[2dqe]], [[2dqf]], [[2dqg]], [[2dqh]], [[2dqi]], [[2dqj]], [[1j1o]], [[1j1p]], [[1j1x]], [[1ic4]], [[1ic5]], [[1ic7]] – HEWL + mLys antibody HYHEL-10 (mutant) 
[[1xgp]], [[1xgq]], [[1xgr]], [[1xgt]], [[1xgu]] – HEWL + mLys antibody HYHEL-63 
[[3d9a]], [[2eks]], [[1ua6]], [[1c08]], [[3hfm]] – HEWL + mLys antibody HYHEL-10 
[[1uac]] - tuLys C + mLys antibody HYHEL-10 
[[1yqv]], [[2iff]] – HEWL + mLys antibody HYHEL-5 
[[1bql]] – BqLys + mLys antibody HYHEL-5 
[[1ndg]] – HEWL + mLys antibody HYHEL-8 
[[1ndm]] – HEWL + mLys antibody HYHEL-26 
[[1dqj]] - HEWL + mLys antibody HYHEL-63 
[[1nby]], [[1nbz]] – HEWL (mutant) + mLys antibody HYHEL-63 
[[1g7h]], [[1g7i]], [[1g7j]], [[1g7l]], [[1g7m]], [[1kip]], [[1kiq]], [[1kir]] – HEWL + mAnti-HEWL monoclonal antibody (mutant) 
[[1mlc]], [[1vfb]] - HEWL + mIGG1-κ D44.1 FAB 
[[1a2y]] - HEWL (mutant) + mIGG1-κ D1.3 FV 
[[1fdl]] - HEWL + mIGG1-κ D1.3 FAB 
[[1jhl]] – phLys + mIGG1-κ D11.15 FV 
[[1fbi]] – GfLys + mIGG1 F9.13.7 FAB 
[[2znw]], [[2znx]] – HEWL + hSCFV10 antibody 
[[1bvk]] - HEWL + hAnti Lys FV antibody 
[[1dzb]] – tuLys + mSCFV 1F9 
[[1zv5]], [[1zvh]], [[1zvy]], [[1zmy]], [[1ri8]], [[1rjc]], [[1xfp]], [[1jtp]], [[1jtt]], [[1jto]], [[1mel]] - HEWL + cAntibody heavy chain domain – camel 
[[1op9]] - hLys C + cAntibody heavy chain domain 
[[3otp]] – HEWL + EcProtease DO – ''Escherichia coli'' 
[[3f6z]] - HEWL + MLIC – ''Pseudomonas aeruginosa'' 
[[3eba]] – hLys C + hCABHUL6 
[[2qb0]], [[2qar]] – T4Lys/E80 TELSAM domain 
[[2i25]], [[2i26]] - HEWL +NsAntigen receptor PBLA8 variable domain – Nurse shark 
[[1sq2]], [[1t6v]] – HEWL +NsNew Antigen receptor variable domain 
[[1gpq]] – HEWL + EcInhibitor of Vertebrate Lys 
[[1aro]] – T7Lys + T7 RNA polymerase 

===Some Useful External Links===
[http://en.wikipedia.org/wiki/Lysozyme Lysozyme]

[http://en.wikipedia.org/wiki/Glycoside_hydrolase#Retaining_glycoside_hydrolases Retaining Glycoside Hydrolases]

===References===
<references/>

Hen Egg-White (HEW) Lysozyme

2011-04-20T18:41:30Z

Anne Goodling:

'''Introduction'''

Lysozyme - also known as muramidase, or glycoside hydrolase - is a powerful enzyme of biological significance found in abundance in tears, saliva, and human milk. In humans, it is encoded in the ''LYZ'' gene. Although it is responsible for the initial digestion of starches in the mouth, it is most widely identified as a non-specific defense in gram positive bacteria and in many species of fungi. Due to its antibacterial effects, it is a strong component of the innate immune system, and is an important part of an infant's diet to ward off diarrheal diseases. Since it is a small, easily available, and highly stable protein containing only 129 amino acid residues, it has been subject to extensive research regarding its function and structure. Hen Egg White (HEW) Lysozyme is shown below.

===History===

Lysozyme is an enzyme known for its unique ability to degrade the polysaccharide architecture of many kinds of cell walls, normally for the purpose of protection against bacterial infection<ref>Lysozyme. 2010. Citizendium.org. http://en.citizendium.org/wiki/Lysozyme</ref>. Its effects were first noticed by Laschtschenko in 1909. It was officially characterized and termed “lysozyme” by Alexander Fleming, the same person credited for the accidental discovery of penicillin.
The characterization of lysozyme in 1922 by Alexander Fleming was providential in that the undertaken experiment related to the discovery of lysozyme was not geared toward any knowledge of such a protein as lysozyme <ref>Lysozyme. 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>. During the unrelated experiment, nasal drippings were inadvertently introduced to a petri dish containing a bacterial culture, which culture consequently exhibited the results of an as yet unknown enzymatic reaction. The observation of this unknown reaction led to further research on the components of this reaction as well as to the corresponding identification of the newfound "lysozyme." Fleming's discovery was complemented by David C. Phillips' 1965 description of the three-dimensional structure of lysozyme via a 200 pm resolution model obtained from X-ray crystallography <ref>Lysozyme, 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>. Phillips' work was especially groundbreaking since Phillips had managed to successfully elucidate the structure of an enzyme via X-ray crystallography - a feat that had never before been accomplished<ref>Bugg, T. 1997. An Introduction to Enzyme and Coenzyme Chemistry. Blackwell Science Ltd., Oxford </ref>. Phillips' research also led to the first sufficiently described enzymatic mechanism of catalytic action <ref>1967. Proc R Soc Lond B Bio 167 (1009): 389–401.</ref>. Thus, Phillips' elucidation of the function of lysozyme led Phillips to reach a more general conclusion on the diversity of enzymatic chemical action in relation to enzymatic structure. Clearly, the findings of Phillips as well as the more general historical development of the understanding of the structure and function of lysozyme have been paramount to the more general realm of enzyme chemistry.

[[Image:nag-nam2.jpg|thumb|left|350px|Lysozyme Cleavage Site]]
<ref>Image from: http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/proteins/lysozyme.htm</ref>

'''Function'''

Lysozyme is known for damaging bacterial cell walls by catalyzing the hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid (NAM) and N-acetyl-D-glucosamine (NAG) residues in peptidoglycan, and between N-acetyl-D-glucosamine residues in chitodextrins. In this way, lysozyme is efficient in lysing the cell walls of both bacteria and fungi. The location of cleavage for lysozyme on this architectural theme is the β(1-4) glycosidic linkage connecting the C1 carbon of NAM to the C4 carbon of NAG.

The particular substrate of preference for this cleavage type is a (NAG-NAM)₃ hexasaccharide, within which substrate occurs the
cleaving target glycosidic bond, NAM₄-β-O-NAG₅. The individual hexasaccharide binding units are designated A-F, with NAM₄-β-O-NAG₅ glycosidic bond cleavage preference corresponding to a D-E unit glycosidic bond cleavage preference.

= Enzymatic Activity of Lysozyme =

Enzymes are designed to attract and to bind specific substrates. The active site of and lysozyme and its specific ligands are described in the following sections

==Mechanistic Features==

'''Zymogen of Lysozyme: Enzymatic Precursor'''

Zymogens are inactive enzyme precursors. Enzymes are developed in an inactive way to prevent the enzyme from digesting the cell that produced it. This process also prevents the enzyme from becoming active in the wrong portion of the body. Lysozyme's zymogen, simply titled “pre-lysozyme,” was sequenced in 1977 by R D Palmiter, J Gagnon, L H Ericsson and K A Walsh, and has since been sequenced much more extensively.

[[Image:jrip.jpg|thumb|left|350px|Mechanism of Lysozyme]]
<ref>Image from: http://www.google.com/imgres?imgurl=http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/pics-and-strucs/lysozyme-mech.gif&imgrefurl=http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/proteins/lysozyme.htm&usg=__ormapG4XKg-tR5GrMSOdSMTV4vE=&h=603&w=801&sz=7&hl=en&start=17&zoom=1&tbnid=nvr9gvFrUILDkM:&tbnh=143&tbnw=189&prev=/images%3Fq%3DThe%2Blysozyme%2Breaction%2Bmechanism%26um%3D1%26hl%3Den%26sa%3DN%26biw%3D1280%26bih%3D647%26tbs%3Disch:10%2C304&um=1&itbs=1&iact=hc&vpx=521&vpy=349&dur=448&hovh=191&hovw=254&tx=140&ty=48&ei=JQ_LTPKzLIjCsAPkzt2KDg&oei=IA_LTP74OsG78gapm-GFAQ&esq=2&page=2&ndsp=18&ved=1t:429,r:2,s:17&biw=1280&bih=647</ref>

'''Mechanism'''

The lysozyme mechanism of action results in the hydrolysis of a glycoside (hence the familial distinction of lysozyme as a glycosylase<ref>Lysozyme, 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>), which corresponds to the conversion of an acetal to a hemiacetal, which reaction (general degradation of glycosidic bond to units "capped" by newly formed hydroxyl groups) necessitates acid catalysis, since the conversion of acetal to hemiacetal involves the protonation of the reactant oxygen prior to actual bond cleavage. <ref>Pratt, C.W., Voet, D., Voet, J.G. Fundamentals of Biochemistry - Life at the Molecular Level - Third Edition. Voet, Voet and Pratt, 2008.</ref>. Furthermore, the transition state obtained from this protonation is a covalent, oxonium ion, intermediate that must obtain resonance stabilization. The need for some means of acid catalysis and covalent resonance stabilization is adequately provided by the Glu 35 and Asp 52 residues of lysozyme, respectively. The reaction mechanism of lysozyme is demonstrated below. In the following image, the reaction begins at the upper left-hand side, and proceeds according to reaction arrows.

As seen to the left, lysozyme works by hydrolyzing the glycosidic bond, distorting the bond between the NAM and NAG. This produces a glycosyl enzyme intermediate, which reacts with a water molecule to produce the product and the unchanged enzyme.

'''Active Site'''

The <scene name='Hen_Egg-White_(HEW)_Lysozyme/Act_site/2'>active site</scene> of lysozyme is formulated as a prominent cleft outlined by the two aforementioned catalytic amino acids, Glu 35 and Asp 52. The active site is geometrically bent to augment ligand binding, and the two amino acids interact with the ligand in the binding site. Asp52 is depicted in red, and Glu35 is depicted in green.

<applet load='1hew' size='350' frame='true' align='right' caption='' />

==Binding==
'''Ligands'''

A ligand is able to bind to the active site of an enzyme to form a biologically relevant complex. The model to the right shows a space-filling model of lysozyme with the protein distinguishable in brown and the ligand distinguishable in green. Another model of the ligand can be seen in this
<scene name='Hen_Egg-White_(HEW)_Lysozyme/Ligand/1'>ribbon diagram</scene>, with the ligand protruding as a space-filling model from the active site. Here, it is clear that the ligand is a polysaccharide.

The lysozyme reaction is characterized by hydrolysis of the beta (1-4) glycosidic bond between NAM and NAG. Lysozyme has a very specific active site, which can bind only six sugar rings from a polysaccharide chain. Once lysozyme binds to this chain, it hydrolyzes them. These six sugar rings represent the ligand of lysozyme. The lysozyme then distorts the fourth sugar in the six-membered complex, producing stress on the molecule and breaking the glycosidic bond.

The amino acid side-chains Glu35 and Asp52 are critical to the activity of this enzyme. Glu35 acts as a proton donor to the glycosidic bond, cleaving the C-O bond in the substrate, and Asp52 acts as a nucleophile to generate a glycosyl enzyme intermediate. The glycosyl enzyme intermediate then reacts with a water molecule to give the product of hydrolysis.

'''Inhibitors'''

Lysozyme is best inhibited by small saccharides which act competitively with the natural substrate. The smaller saccharides will bind to the first three binding sites of the cleft (sites A-C), but will not reach sites D and E, where the enzyme cuts the glycosidic bond. So, the competitive inhibitor will stick in the cleft, not allowing the substrate to bind to the enzyme complex.<ref>http://mcdb-webarchive.mcdb.ucsb.edu/sears/biochemistry/tw-enz/lysozyme/HEWL/lysozyme-overview.htm</ref> Several known inhibitors of lysozyme are: SDS, N-acetyl-D-glucosamine, and various alcohols and oxidizing agents.<ref>http://www.worthington-biochem.com/ly/default.html</ref>

<applet load='1hew' size='350' frame='true' align='left' caption='' />

= Composition and Structure of Lysozyme =

All proteins consist of carbon, hydrogen, nitrogen, oxygen, and sulfur, as do most organic molecules. Enzymes are composed in such a way as to maximize their reactivity with their desired substrate, increasing the efficiency of biological reactions. The <scene name='Sandbox_39/Elements/1'>composition of lysozyme</scene> can be seen on the left, with the carbon atoms outlined in gray, oxygen atoms in red, nitrogen atoms in blue, sulfur atoms in yellow, and the three-letter abbreviation for the <scene name='Sandbox_39/Amino_acid_residues/1'>amino acid residues</scene> in purple.

Lysozyme, like all proteins, also contains a <scene name='Sandbox_39/C_and_n_terminal_residues/1'> 3'C and 5'N terminal </scene>, and these can be seen by following the colors of the rainbow across the molecule. Starting at the red end, the 3' C terminal end, one can work the entire way through to the 5' N terminal end, showing the folding pattern and chain of the protein.

== Secondary Structure ==

Lysozyme contains five <scene name='Sandbox_38/A/2'>alpha helical</scene> regions and five regions containing <scene name='Sandbox_38/B/1'>beta sheets</scene> as displayed in this <scene name='Sandbox_38/Alphab/1'>image</scene>. Linking these secondary structures, a number of beta turns and a large number of random coils make up the remainder of the polypeptide backbone. The polypeptide backbone of lysozyme involved in the 3 antiparallel beta sheets display the beta hairpin motif of supersecondary structure. This depiction of lysozyme contains an antiparallel beta-pleated sheet, which contributes greatly to the stability of the molecule by providing the correct alignment of hydrogen bonds. Lysozyme also contains a great deal of random coil, which is seen in the white regions of the molecule.

'''Hydrogen Bonding'''

In all proteins <scene name='Sandbox_39/Hydrogen_bonds/2'>hydrogen bonds</scene> are essential for stability. In this ribbon diagram, the hydrogen bonds can be seen between the secondary structures of lysozyme highlighted in orange. Since the double bonds of the alpha carbons in the main chain of lysozyme cause torsional strain, lysozyme is limited to very specific hydrogen bonding between the amino acid residues. This representation clearly shows how crucial hydrogen bonding is to help maintain the stability of the protein.

==Amino Acid Residues==

The amino acids present in the lysozyme polypeptide sequence have a direct influence not only on primary structure, but also on the secondary and tertiary structures, which can be influenced by polarity and charge of the sidechains. The various amino acid residues
differ in their properties because of the great variety of side chains present on each amino acid. Polar and nonpolar (and charged and uncharged) side chains lead to various degrees of hydrophobicity and hydrophilicity, which affects protein folding. In lysozyme, the <scene name='Hen_Egg-White_(HEW)_Lysozyme/Residue/1'>residues</scene> that interact with substrate are displayed.

= Bonding Interactions =

'''Disulfide Bonding in Lysozyme'''

Lysozyme contains four <scene name='Sandbox_39/Disulfide_bonds/1'>disulfide bonds</scene> involving eight cysteine residues, which are highlighted in yellow on the left. Disulfide bonds are intramolecular forces that stabilize the tertiary structure of many proteins. Disulfide bonds are present in four locations in lysozyme: between Cys 6 and Cys 127, between Cys 30 and Cys 115, between Cys 64 and Cys 80 and between Cys 76 and Cys 94.

<applet load='1hew' size='350' frame='true' align='left' caption='' />

= Intermolecular Interactions =

'''Hydrophobicity'''

Lysozyme contains both hydrophobic and hydrophilic <scene name='Hen_Egg-White_(HEW)_Lysozyme/Pink_polar/1'>regions</scene>( <scene name='Sandbox_39/Hydrophobicity/2'>Hydrophobicity</scene> ). The hydrophilic effect, or the desire for proteins to be at a specific position regarding water, is the single most important determinant of protein folding. These regions can be displayed with the hydrophobic regions in gray and the polar, hydrophillic regions in purple. This coloration highlights the location of these regions, showing that the majority of the hydrophobic regions are inside of the protein and that the majority of the hydrophillic regions are on the outside of the protein.

'''Polarity'''

The nature of the amino acid sidechains in the lysozyme polypeptide sequence leads to regions of varying hydrophobicities and polarities of the enzyme structure. The presence of certain regions of hydrophilicity and hydrophobicity is a driving force in determining protein structure when folding. The varying polarities of the side chains influence the locations of residues in the enzyme structure. Nonpolar residues appear blue, and polar residues appear red in the following <scene name='Sandbox_38/Non_polar_blue/1'>polarity</scene> display of lysozyme. Nonpolar residues will display hydrophobic tendencies occurring mostly on the interior of the enzyme while polar residues will increase in abundance on the surface of the protein in order to increase contact with the aqueous solvent so as to satisfy their hydrophilic nature. By observing a space-filled structural depiction of <scene name='Sandbox_38/Non_polar_blu/1'>lysozyme polarity</scene> with polar molecules colored red and nonpolar molecules colored blue the influence of polarity on nucleotide arrangement and protein folding is evident, with the blue (nonpolar) regions inside the red (polar) regions. The presence of <scene name='Sandbox_39/Water/1'>water</scene> interacting with the various hydrophilic residues is depicted to further display how polarity affects structure. Water is depicted as yellow, and the polar and nonpolar regions remain their respective color.

'''Charge'''

Charges of the various regions of the lysozyme structure display a hydrophilic nature and thus also affect the location of that region of polypeptides and the overall folding of the protein. Charged regions of the protein will display hydrophilic tendencies and therefore will most often be located on the surface of the lysozyme molecule where they can interact with the aqueous solvent. Non-charged portions will display hydrophobic tendencies and be located on the interior of the molecule. The effect of various <scene name='Sandbox_38/Rb/1'>charges</scene> on protein structure can be visualized with charged molecules represented by red anionic and blue cationic regions, and uncharged regions colored in grey. This depiction of lysozyme uses a spacefill representation of lysozyme to depict <scene name='Sandbox_38/Chargeddd/1'>charges</scene>.

= Applications of Lysozyme =

Since lysozyme has been widely recognized for its antibacterial and antifungal properties, it has a wide variety of uses both in biochemical and pharmaceutical applications. In molecular biology, lysozyme is often used in the alkaline-lysis procedure for extracting and isolating plasmid DNA. It is used extensively in the pharmaceutical field for destroying gram-positive bacteria, and can be used to support already-existing immune defenses to fight bacterial infections. This enzyme is particularly important for preventing bacterial diseases in infants. Because of its antibacterial properties, lysozyme can also be used in the food industry to help prevent spoilage of foods.

= Discovery and Applications of Hen Egg-White Lysozyme=

<applet load='aln_1H6M_to_1HEW_2.pdb' size='300' frame='true' align='right' caption=' Hen Egg White (HEW) Lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to the active site, PDBid 1HEW' scene='User:Judy_Voet/Lysozyme/Lysozyme1/16' />
Lysozyme was the first enzyme whose X-ray structure was determined <ref> PMID 5840126</ref><ref>Phillips, D. C. The hen egg white lysozyme molecule. Proc. Natl Acad. Sci. USA 57, 483-495 (1967)</ref>. This <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>scene </scene> shows Hen Egg White (HEW) lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to a cleft in the enzyme. David Phillips, who determined the structure in 1965, saw that the cleft was large enough to fit three more saccharide units.
He therefore built a model extending the trisaccharide to a
<scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> that fits into the cleft, labeling the sugar subsites A-F<ref> coordinates of the model kindly provided by Louise Johnson</ref>. Alternately click on <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>trisaccharide</scene> and <scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> to turn the modeled portion of the hexasaccharide on and off.

The interesting thing about the model was that the only way that the hexasaccharide would fit into the cleft was if the 4th saccharide (in subsite D) was strained into a <scene name='User:Judy_Voet/Lysozyme/Half-chair/2'>half-chair conformation</scene>. This conformation is what would be necessary for the formation of an oxocarbenium ion (oxionium ion). When the model was studied, <scene name='User:Judy_Voet/Lysozyme/Glu_35/1'>Glu 35</scene> was found to be in an ideal location to act as a general acid catalyst, 3.34 Angstroms from the bridging oxygen between the 4th and 5th saccharide units. <scene name='User:Judy_Voet/Lysozyme/Asp_52/2'>Asp 52</scene> appeared to be too far away (2.69 angstroms) in the static lysozyme structure to have formed a covalent bond with C1 of the half-chair model in the D site, and no covalent intermediate had ever been detected, so Phillips proposed that it acted as an electrostatic stabilizer of the oxonium ion (referred to as The Phillips Mechanism).

<applet load='aln_1H6M_to_1HEW_2.pdb' size='200' frame='true' align='left' caption='NAG-2-deoxy-2-fluoro-glucosyl fluoride (NAG2FGlcF) bound to Glu35Gln HEW Lysozyme PDBid 1H6M' scene='User:Judy_Voet/Lysozyme/1h6m/3'/>

Then, in 2001, Stephen Withers published <scene name='User:Judy_Voet/Lysozyme/1h6m/3'>1H6M</scene>,<ref>PMID 11518970</ref> in which Glu 35 had been mutated to Gln to remove the general acid catalyst. The substrate contained NAG-2-fluoro-glucosyl fluoride (NAG2FGlcF). The fluoro group on C-1 does not require acid catalysis to be a good leaving group, and the remaining saccharide, in the absence of the acid necessary to catalyse the second step of the reaction, was demonstrated to form a <scene name='User:Judy_Voet/Lysozyme/Covalent/1'> covalent intermediate</scene>. In this <scene name='User:Judy_Voet/Lysozyme/Superposition/2'>superposition</scene> of the half chair model with 1HEW (greens) and the covalent intermediate in 1H6M (blues), note the relatively small motions of Asp 52 and C1 of the sugar ring in going from the model to the covalent intermediate. to observe the motion from the <scene name='User:Judy_Voet/Lysozyme/Asp52_halfchair/1'>half-chair</scene> to the <scene name='User:Judy_Voet/Lysozyme/Covalent/2'>covalent intermediate</scene> just toggle between the two green links.

== 3D Structures of Lysozyme ==

===Lys===

[[2x0a]], [[3iju]], [[3ijv]], [[3a8z]], [[2w1y]], [[2w1m]], [[2w1x]], [[2w1l]], [[3e3d]], [[3exd]], [[2zq3]], [[2zq4]], [[3b72]], [[3b6l]], [[2z12]], [[2z18]], [[2z19]], [[2vb1]], [[2hu3]], [[2hub]], [[2htx]], [[2hu1]], [[2yvb]], [[2epe]], [[2g4p]], [[2g4q]], [[2cgi]], [[2b5z]], [[2d4k]], [[2d91]], [[2f2n]], [[2fbb]], [[2c8o]], [[2c8p]], [[2a6u]], [[2aub]], [[2blx]], [[2bly]], [[2a7d]], [[2a7f]], [[1wtm]], [[1wtn]], [[1w6z]], [[1vdp]], [[1vdq]], [[1vds]], [[1vdt]], [[1ved]], [[1v7t]], [[1ps5]], [[2cds]], [[1lj3]], [[1lj4]], [[1lje]], [[1ljf]], [[1ljg]], [[1ljh]], [[1lji]], [[1ljj]], [[1ljk]], [[1jis]], [[1jit]], [[1jiy]], [[1jj0]], [[1jj1]], [[1jj3]], [[1iee]], [[1qio]], [[1f0w]], [[1f10]], [[1dpx]], [[1c10]], [[1qtk]], [[1lz8]], [[1lz9]], [[1bhz]], [[1bgi]], [[1bwh]], [[1bwi]], [[1bwj]], [[1bvx]], [[1hsw]], [[1hsx]], [[1lpi]], [[4lzt]], [[3lzt]], [[1aki]], [[1jpo]], [[1rfp]], [[193l]], [[194l]], [[5lym]], [[1lza]], [[3lyt]], [[4lyt]], [[5lyt]], [[6lyt]], [[2lzt]], [[1lzt]], [[1lzh]], [[2lzh]], [[7lyz]], [[1lyz]], [[2lyz]], [[3lyz]], [[4lyz]], [[5lyz]], [[6lyz]] - HEWL – chicken 
[[1xei]], [[1xej]], [[1xek]], [[1uco]], [[1lma]], [[4lym]] – HEWL low hydration 
[[1lsa]], [[1lsb]], [[1lsc]], [[1lsd]], [[1lse]], [[1lsf]], [[1lys]] – HEWL temperature influence 
[[2lym]], [[3lym]] – HEWL pressure influence 
[[132l]] – HEWL methylated 
[[1rcm]] – HEWL 3 S-S form 
[[2xbr]], [[2xbs]]- HEWL– Raman crystallography 
[[2zwb]], [[1io5]], [[1lzn]] - HEWL– Neutron 
[[1gxv]], [[1gxx]], [[1e8l]] - HEWL- NMR 
[[2hs7]], [[2hso]], [[2hs9]]- HEWL– Powder diffraction 
[[1ir7]], [[1ir8]], [[1ir9]], [[1ioq]], [[1ior]], [[1ios]], [[1iot]], [[1flq]], [[1flu]], [[1flw]], [[1fly]], [[1fn5]], [[1kxw]], [[1kxx]], [[1kxy]], [[1uia]], [[1uib]], [[1uic]], [[1uid]], [[1uie]], [[1uif]], [[1uig]], [[1uih]], [[1lsm]], [[1lsn]], [[1hel]], [[1hem]], [[1hen]], [[1heo]], [[1hep]], [[1heq]], [[1her]] – HEWL (mutant) 
[[1lyo]], [[2lyo]], [[3lyo]], [[4lyo]] – HEWL cross-linked 
[[1xft]] - tuLys – turkey - Powder diffraction 
[[1jse]], [[1tew]], [[135l]], [[2lz2]], [[1lz2]] – tuLys 
[[3lz2]] – tuLys - Laue 
[[3ab6]] – Lys + NAG3 – Hard clam 
[[2x8r]] – Lys GH25 – ''Aspergillus fumigatus'' 
[[3mgw]] – Lys G – Atlantic salmon 
[[3gxk]], [[3gxr]] – Lys G + NAG – Atlantic cod 
[[2fbd]] – HfLys 1 
[[3cb7]] – HfLys 2 
[[2zij]], [[2zik]], [[2zil]], [[2nwd]], [[1iwt]], [[1iwu]], [[1iwv]], [[1iww]], [[1iwx]], [[1iwy]], [[1iwz]], [[1jwr]], [[1jsf]], [[1rex]], [[1lz1]] – hLys – human 
[[1w08]], [[1ix0]], [[1ioc]], [[1ip1]], [[1ip2]], [[1ip3]], [[1ip4]], [[1ip5]], [[1ip6]], [[1ip7]], [[1qsw]], [[1gev]], [[1gez]], [[1gf0]], [[1gf3]], [[1gf4]], [[1gf5]], [[1gf6]], [[1gf7]], [[1i1z]], [[1i20]], [[1i22]], [[1gfr]], [[1gft]], [[1gfu]], [[1gfv]], [[1gf8]], [[1gf9]], [[1gfa]], [[1gfe]], [[1gfg]], [[1gfh]], [[1gfj]], [[1gfk]], [[1inu]], [[1gdx]], [[1ge0]], [[1ge1]], [[1ge2]], [[1ge3]], [[1ge4]], [[1gdw]], [[1gaz]], [[1gb0]], [[1gb2]], [[1gb3]], [[1gb5]], [[1gb6]], [[1gb7]], [[1gb8]], [[1gb9]], [[1gbo]], [[1gbw]], [[1gbx]], [[1gby]], [[1gbz]], [[1gay]], [[1eq4]], [[1eq5]], [[1eqe]], [[1c7p]], [[1di3]], [[1di4]], [[1di5]], [[1c43]], [[1c45]], [[1c46]], [[1ckg]], [[1cj6]], [[1cj7]], [[1cj8]], [[1cj9]], [[1ckc]], [[1ckd]], [[1ckf]], [[1ckh]], [[1b5z]], [[1b70]], [[1b7q]], [[1b7r]], [[1b7s]], [[1b7l]], [[1b7m]], [[1b7n]], [[1b7p]], [[1b5u]], [[1b5v]], [[1b5w]], [[1b5x]], [[1b5y]], [[1bb3]], [[1bb4]], [[2bqa]], [[2bqb]], [[2bqc]], [[2bqd]], [[2bqe]], [[2bqf]], [[2bqg]], [[2bqh]], [[2bqi]], [[2bqj]], [[2bqk]], [[2bql]], [[2bqm]], [[2bqn]], [[2bqo]], [[2mea]], [[2meb]], [[2mec]], [[2med]], [[2mee]], [[2mef]], [[2meg]], [[2meh]], [[2mei]], [[1wqm]], [[1wqn]], [[1wqo]], [[1wqp]], [[1wqq]], [[1wqr]], [[2heb]], [[2hea]], [[2hec]], [[2hed]], [[2hee]], [[2hef]], [[1jka]], [[1jkb]], [[1jkc]], [[1jkd]], [[1loz]], [[1lyy]], [[1oua]], [[1oub]], [[1ouc]], [[1oud]], [[1oue]], [[1ouf]], [[1oug]], [[1ouh]], [[1oui]], [[1ouj]], [[207l]], [[208l ]], [[1yam]], [[1yan]], [[1yao]], [[1yap]], [[1yaq]], [[1lmt]], [[1lhh]], [[1lhi]], [[1lhj]], [[1lhk]], [[1lhl]], [[133l]], [[134l]], [[1lz4]], [[1lz5]], [[1lz6]], [[1laa]], [[1tay]], [[1tby]], [[1tcy]], [[1tdy]], [[2lhm]], [[3lhm]] – hLys (mutant) 
[[1iy3]], [[1iy4]] – hLys - NMR 
[[2z2f]] – Lys – Bovine 
[[2cwi]], [[1el1]], [[1qqy]] – dLys - dog 
[[2z2e]] – dLys (mutant) 
[[1i56]] – dLys – NMR 
[[2dqa]] – Lys – ''Tapes japonica'' 
[[2gv0]] – Lys – Soft-shelled turtle 
[[1ivm]] – mLys M – NMR – mouse 
[[1jfx]] – Lys – ''Streptomyces coelicolor'' 
[[1gd6]] – Lys – ''Bombyx mori'' 
[[1jug]] – Lys – Echidna 
[[1dkj]] – BqLys – Bobwhite quail 
[[2ihl]] – Lys – Japanese quail 
[[1gbs]] – BsLys – Black swan 
[[1lmn]] – RtLys – Rainbow trout 
[[2eql]] – Lys – horse 
[[1ghl]] – phLys – pheasant 
[[1hhl]] – GfLys – Guinea fowl 
[[1lhm]] – Lys (mutant) – yeast 

===Lys small molecules complexes===

[[3fe0]], [[2d4i]], [[2d4j]], [[1v7s]] - HEWL+ D2O 
[[3m3u]] – HEWL Trp fluorescence 
[[2xjw]] - HEWL + CO 
[[1hf4]], [[1lks]] – HEWL + NO3 
[[3a34]], [[3ems]] - HEWL + arginine 
[[2xth]] – cLys + inhibitor K2PtBr6 
[[3a90]], [[3a91]], [[3a92]], [[3a93]], [[3a94]], [[3a95]], [[3a96]], [[3kam]], [[2pc2]], [[2bpu]], [[1t3p]], [[1h87]] – HEWL + rare earth 
[[2d6b]], [[2hg0]], [[1vat]], [[1gwd]], [[1b2k]], [[1lkr]], [[1azf]], [[8lyz]]- HEWL+ halogen 
[[1vat]] - HEWL + Xe 
[[1n4f]] - HEWL + As 
[[2i6z]] - HEWL + Pt drug 
[[2zyp]] - HEWL + poly (allyl amine) 
[[2f30]], [[2f4a]] – HEWL + urea derivative 
[[2f4g]], [[1ykx]], [[1yky]], [[1ykz]], [[1yl0]], [[1yl1]], [[1z55]] - HEWL + alcohol 
[[1dpw]] – HEWL + MPD 
[[1lcn]] – HEWL + SCN 
[[2zxs]] - HEWL with glycine-amide 
[[2h9j]], [[2h9k]], [[1yik]], [[1yil]] - HEWL + cyclam derivative 
[[1b0d]] – HEWL + p-toluene-sulfonate 
[[2q0m]] - HEWL + tricarbonylmanganese 
[[2war]] – HEWL (mutant) + chitopentaose 
[[2h5z]] – HfLys 1 + chitotetraose – House fly 
[[1hnl]] – hLys + glutathione 
[[1dkk]] – BqLys + NO3 

===Lys complex with glucoside===

[[3a3q]] – HEWL (mutant) + NAG 
[[1sf4]], [[1sf6]], [[1sf7]], [[1sfb]], [[1sfg]], [[1ja2]], [[1ja4]], [[1ja6]], [[1ja7]] – HEWL + NAG oligosaccharide – Powder diffraction 
[[1ubz]], [[1d6p]], [[1d6q]], [[1bb5]] – hLys (mutant) + glycoside 
[[1uc0]], [[1re2]], [[1rem]], [[1rey]], [[1rez]], [[1lzr]], [[1lzs]] - hLys + glycoside 
[[1ljn]], [[1jef]], [[1lzy]] – tuLys + glycoside 
[[1h6m]], [[1at5]], [[1at6]], [[1lzb]], [[1lzc]], [[1lzd]], [[1lze]], [[1lzg]], [[1hew ]]– HEWL + glycoside 
[[1lsy]], [[1lsz]] - HEWL (mutant) + glycoside 
[[1bb6]], [[1bb7]] – RtLys + glycoside 
[[1lmc]] – RtLys + bulgecin 
[[1lmo]], [[1lmp]], [[1lmq]] – RtLys + glucoside 
[[1lsp]] – BsLys + bulgecin 
[[153l]], [[154l]] – Lys +glucoside – goose 

===Phage Lys===

[[2oe4]], [[2oe7]], [[2oe9]], [[2oea]], [[1swz]], [[1cx6]], [[1qtc]], [[1qtd]], [[1qth]], [[1qsb]], [[1qs5]], [[1qs9]], [[1qtb]], [[256l]], [[206l]], [[167l]], [[168l]], [[169l]], [[170l]], [[171l]], [[172l]], [[173l]], [[174l]], [[175l]], [[176l]], [[177l]], [[178l]], [[181l]], [[182l]], [[183l]], [[184l]], [[185l]], [[186l]], [[187l]], [[188l]], [[1nhb]], [[137l]], [[216l]], [[152l]], [[149l]], [[150l]], [[151l]], [[1lyd]], [[2lzm]] - T4Lys – Enterobacteria phage T4 
[[138l]] – T4Lys cross-linked 
[[4lzm]], [[5lzm]], [[6lzm]], [[7lzm]] – T4Lys ionic strength 
[[3l2x]], [[3k2r]], [[3g3v]], [[3g3w]], [[3g3x]], [[2q9d]], [[2q9e]], [[2igc]], [[2ntg]], [[2nth]], [[2ou8]], [[2ou9]], [[1zur]], [[1zwn]], [[1zyt]], [[2cuu]], [[2a4t]] – T4Lys (mutant) spin labeled 
[[3l64]], [[3hwl]], [[3jr6]], [[3gui]], [[3c7w]], [[3c7y]], [[3c7z]], [[3c80]], [[3c81]], [[3c82]], [[3c83]], [[3c8q]], [[3c8r]], [[3c8s]], [[3cdo]], [[3cdq]], [[3cdr]], [[3cdt]], [[3cdv]], [[3f8v]], [[3f9l]], [[3fa0]], [[3fad]], [[3fi5]], [[3dke]], [[3dmv]], [[2o4w]], [[2o79]], [[2o7a]], [[2huk]], [[2hul]], [[2hum]], [[2b7x]], [[2b6t]], [[2b6w]], [[2b6x]], [[2b6y]], [[2b6z]], [[2b70]], [[2b72]], [[2b73]], [[2b74]], [[2b75]], [[1sx7]], [[1swy]], [[1sx2]], [[1t6h]], [[1ssw]], [[1ssy]], [[1t8f]], [[1t8g]], [[1t8a]], [[1t97]], [[1p56]], [[1p5c]], [[1p2l]], [[1p2r]], [[1p36]], [[1p37]], [[1p3n]], [[1p46]], [[1p64]], [[1p6y]], [[1p7s]], [[1pqd]], [[1pqi]], [[1pqj]], [[1pqk]], [[1pqm]], [[1pqo]], [[1oyu]], [[1ks3]], [[1kw5]], [[1kw7]], [[1ky0]], [[1ky1]], [[1l0j]], [[1l0k]], [[1lw9]], [[1lwg]], [[1lwk]], [[1lpy]], [[1llh]], [[1lgu]], [[1li6]], [[1jtm]], [[1jtn]], [[1jqu]], [[1kni]], [[1g06]], [[1g07]], [[1g0g]], [[1g0j]], [[1g0k]], [[1g0l]], [[1g0m]], [[1g0p]], [[1g0q]], [[1g1v]], [[1g1w]], [[1i6s]], [[257l]], [[258l]], [[260l]], [[1epy]], [[1b6i]], [[1cu6]], [[1d9w]], [[1ctw]], [[1cu0]], [[1cu2]], [[1cu3]], [[1cu5]], [[1cv1]], [[1cv4]], [[1cv5]], [[1cv6]], [[1cvk]], [[1cx7]], [[1d2w]], [[1d2y]], [[1d3f]], [[1d3j]], [[1d3m]], [[1d3n]], [[1cv3]], [[1qt3]], [[1qt4]], [[1qt5]], [[1qt6]], [[1qt7]], [[1qt8]], [[1qtv]], [[1qtz]], [[1qud]], [[1qug]], [[1quh]], [[1quo]], [[1qsq]], [[261l]], [[262l]], [[259l]], [[220l]], [[222l]], [[223l]], [[225l]], [[226l]], [[227l]], [[228l]], [[229l]], [[235l]], [[236l]], [[237l]], [[238l]], [[239l]], [[240l]], [[241l]], [[242l]], [[243l]], [[244l]], [[245l]], [[246l]], [[247l]], [[248l]], [[249l]], [[250l]], [[251l]], [[252l]], [[253l]], [[254l]], [[255l]], [[230l]], [[231l]], [[232l]], [[233l]], [[234l]], [[209l]], [[210l]], [[211l]], [[212l]], [[213l]], [[214l]], [[215l]], [[218l]], [[219l]], [[180l]], [[195l]], [[196l]], [[197l]], [[198l]], [[199l]], [[200l]], [[190l]], [[191l]], [[192l]], [[189l]], [[155l]], [[156l]], [[157l]], [[158l]], [[159l]], [[160l]], [[161l]], [[162l]], [[163l]], [[164l]], [[165l]], [[166l]], [[129l]], [[130l]], [[131l]], [[140l]], [[141l]], [[142l]], [[143l]], [[144l]], [[145l]], [[146l]], [[147l]], [[201l]], [[205l]], [[221l]], [[224l]], [[102l]], [[103l]], [[104l]], [[107l]], [[108l]], [[109l]], [[110l]], [[111l]], [[112l]], [[113l]], [[114l]], [[115l]], [[118l]], [[119l]], [[120l]], [[122l]], [[123l]], [[125l]], [[126l]], [[127l]], [[128l]], [[1dya]], [[1dyb]], [[1dyc]], [[1dyd]], [[1dye]], [[1dyf]], [[1dyg]], [[1l00]], [[1l85]], [[1l86]], [[1l87]], [[1l88]], [[1l89]], [[1l90]], [[1l91]], [[1l92]], [[1l93]], [[1l94]], [[1l95]], [[1l96]], [[1l97]], [[1l98]], [[1l99]], [[1lye]], [[1lyf]], [[1lyg]], [[1lyh]], [[1lyi]], [[1lyj]], [[217l]], [[1tla]], [[1l77]], [[1l79]], [[1l80]], [[1l81]], [[1l82]], [[2l78]], [[1l36]], [[1l37]], [[1l38]], [[1l39]], [[1l40]], [[1l41]], [[1l42]], [[1l43]], [[1l44]], [[1l45]], [[1l46]], [[1l47]], [[1l48]], [[1l49]], [[1l50]], [[1l51]], [[1l52]], [[1l53]], [[1l54]], [[1l55]], [[1l56]], [[1l57]], [[1l58]], [[1l59]], [[1l60]], [[1l61]], [[1l62]], [[1l63]], [[1l64]], [[1l65]], [[1l66]], [[1l67]], [[1l68]], [[1l69]], [[1l70]], [[1l71]], [[1l72]], [[1l73]], [[1l74]], [[1l75]], [[1l76]], [[1l17]], [[1l18]], [[1l19]], [[1l20]], [[1l21]], [[1l22]], [[1l23]], [[1l24]], [[1l25]], [[1l26]], [[1l27]], [[1l28]], [[1l29]], [[1l30]], [[1l31]], [[1l32]], [[1l33]], [[1l34]], [[1l35]], [[3lzm]], [[1l01]], [[1l02]], [[1l03]], [[1l04]], [[1l05]], [[1l06]], [[1l07]], [[1l08]], [[1l09]], [[1l10]], [[1l11]], [[1l12]], [[1l13]], [[1l14]], [[1l15]], [[1l16]] – T4Lys (mutant) 
[[1c60]], [[1c61]], [[1c62]], [[1c63]], [[1c64]], [[1c65]], [[1c66]], [[1c67]], [[1c68]], [[1c69]], [[1c6a]], [[1c6b]], [[1c6c]], [[1c6d]], [[1c6e]], [[1c6f]], [[1c6g]], [[1c6h]], [[1c6i]], [[1c6j]], [[1c6k]], [[1c6l]], [[1c6m]], [[1c6n]], [[1c6p]], [[1c6q]], [[1c6t]] - T4Lys (mutant) + noble gas 
[[3ht6]], [[3ht7]], [[3ht8]], [[3ht9]], [[3htb]], [[3hu8]], [[3huq]], [[3guj]], [[3guk]], [[3gul]], [[3gum]], [[3gun]], [[3guo]], [[3gup]], [[3dmx]], [[3dmz]], [[3dn0]], [[3dn1]], [[3dn2]], [[3dn3]], [[3dn4]], [[3dn6]], [[3dn8]], [[3dna]], [[2rb1]], [[2ray]], [[2raz]], [[2rb0]], [[2rb2]], [[2rbn]], [[2rbo]], [[2rbq]], [[2rbr]], [[2rbs]], [[2oty]],[[2otz]], [[1owy]], [[1owz]], [[1ov5]], [[1ov7]], [[1ovh]], [[1ovj]], [[1ovk]], [[1lgw]], [[1lgx]], [[1li2]], [[1li3]], [[1l83]], [[1l84]] – T4Lys (mutant) + benzene derivative 
[[3htd]], [[3htf]], [[3htg]], [[3hu9]], [[3hua]], [[3huk]], [[3hh3]], [[3hh4]], [[3hh5]], [[3hh6]], [[2rbp]], [[2ou0]], [[2f2q]], [[2f32]], [[2f47]], [[1xep]] – T4Lys (mutant) + inhibitor 
[[148l]] - T4Lys (mutant) + glucoside 
[[3d3d]], [[1d9u]] – lamLys + chitohexasaccharide 
[[1am7]] – lamLys - Enterobacteria phage λ 
[[2anv]], [[2anx]] – Lys (mutant)]] - Enterobacteria phage p22 
[[1xjt]], [[1xju]] - Lys - Enterobacteria phage p1 
[[1lba]] - T7Lys - Enterobacteria phage T7 

===Lys protein complex===

[[3m18]], [[3g3a]], [[3g3b]] - HEWL + Variable lymphocyte receptor – Marine lamprey 
[[3a67]], [[3a6b]], [[3a6c]], [[2yss]], [[2eiz]], [[2dqc]], [[2dqd]], [[2dqe]], [[2dqf]], [[2dqg]], [[2dqh]], [[2dqi]], [[2dqj]], [[1j1o]], [[1j1p]], [[1j1x]], [[1ic4]], [[1ic5]], [[1ic7]] – HEWL + mLys antibody HYHEL-10 (mutant) 
[[1xgp]], [[1xgq]], [[1xgr]], [[1xgt]], [[1xgu]] – HEWL + mLys antibody HYHEL-63 
[[3d9a]], [[2eks]], [[1ua6]], [[1c08]], [[3hfm]] – HEWL + mLys antibody HYHEL-10 
[[1uac]] - tuLys C + mLys antibody HYHEL-10 
[[1yqv]], [[2iff]] – HEWL + mLys antibody HYHEL-5 
[[1bql]] – BqLys + mLys antibody HYHEL-5 
[[1ndg]] – HEWL + mLys antibody HYHEL-8 
[[1ndm]] – HEWL + mLys antibody HYHEL-26 
[[1dqj]] - HEWL + mLys antibody HYHEL-63 
[[1nby]], [[1nbz]] – HEWL (mutant) + mLys antibody HYHEL-63 
[[1g7h]], [[1g7i]], [[1g7j]], [[1g7l]], [[1g7m]], [[1kip]], [[1kiq]], [[1kir]] – HEWL + mAnti-HEWL monoclonal antibody (mutant) 
[[1mlc]], [[1vfb]] - HEWL + mIGG1-κ D44.1 FAB 
[[1a2y]] - HEWL (mutant) + mIGG1-κ D1.3 FV 
[[1fdl]] - HEWL + mIGG1-κ D1.3 FAB 
[[1jhl]] – phLys + mIGG1-κ D11.15 FV 
[[1fbi]] – GfLys + mIGG1 F9.13.7 FAB 
[[2znw]], [[2znx]] – HEWL + hSCFV10 antibody 
[[1bvk]] - HEWL + hAnti Lys FV antibody 
[[1dzb]] – tuLys + mSCFV 1F9 
[[1zv5]], [[1zvh]], [[1zvy]], [[1zmy]], [[1ri8]], [[1rjc]], [[1xfp]], [[1jtp]], [[1jtt]], [[1jto]], [[1mel]] - HEWL + cAntibody heavy chain domain – camel 
[[1op9]] - hLys C + cAntibody heavy chain domain 
[[3otp]] – HEWL + EcProtease DO – ''Escherichia coli'' 
[[3f6z]] - HEWL + MLIC – ''Pseudomonas aeruginosa'' 
[[3eba]] – hLys C + hCABHUL6 
[[2qb0]], [[2qar]] – T4Lys/E80 TELSAM domain 
[[2i25]], [[2i26]] - HEWL +NsAntigen receptor PBLA8 variable domain – Nurse shark 
[[1sq2]], [[1t6v]] – HEWL +NsNew Antigen receptor variable domain 
[[1gpq]] – HEWL + EcInhibitor of Vertebrate Lys 
[[1aro]] – T7Lys + T7 RNA polymerase 

===Some Useful External Links===
[http://en.wikipedia.org/wiki/Lysozyme Lysozyme]

[http://en.wikipedia.org/wiki/Glycoside_hydrolase#Retaining_glycoside_hydrolases Retaining Glycoside Hydrolases]

===References===
<references/>

Hen Egg-White (HEW) Lysozyme

2011-04-20T18:34:17Z

Anne Goodling:

'''Introduction'''

Lysozyme - also known as muramidase, or glycoside hydrolase - is a powerful enzyme of biological significance found in abundance in tears, saliva, and human milk. In humans, it is encoded in the ''LYZ'' gene. Although it is responsible for the initial digestion of starches in the mouth, it is most widely identified as a non-specific defense in gram positive bacteria and in many species of fungi. Due to its antibacterial effects, it is a strong component of the innate immune system, and is an important part of an infant's diet to ward off diarrheal diseases. Since it is a small, easily available, and highly stable protein containing only 129 amino acid residues, it has been subject to extensive research regarding its function and structure. Hen Egg White (HEW) Lysozyme is shown below.

===History===

Lysozyme is an enzyme known for its unique ability to degrade the polysaccharide architecture of many kinds of cell walls, normally for the purpose of protection against bacterial infection<ref>Lysozyme. 2010. Citizendium.org. http://en.citizendium.org/wiki/Lysozyme</ref>. Its effects were first noticed by Laschtschenko in 1909. It was officially characterized and termed “lysozyme” by Alexander Fleming, the same person credited for the accidental discovery of penicillin.
The characterization of lysozyme in 1922 by Alexander Fleming was providential in that the undertaken experiment related to the discovery of lysozyme was not geared toward any knowledge of such a protein as lysozyme <ref>Lysozyme. 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>. During the unrelated experiment, nasal drippings were inadvertently introduced to a petri dish containing a bacterial culture, which culture consequently exhibited the results of an as yet unknown enzymatic reaction. The observation of this unknown reaction led to further research on the components of this reaction as well as to the corresponding identification of the newfound "lysozyme." Fleming's discovery was complemented by David C. Phillips' 1965 description of the three-dimensional structure of lysozyme via a 200 pm resolution model obtained from X-ray crystallography <ref>Lysozyme, 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>. Phillips' work was especially groundbreaking since Phillips had managed to successfully elucidate the structure of an enzyme via X-ray crystallography - a feat that had never before been accomplished<ref>Bugg, T. 1997. An Introduction to Enzyme and Coenzyme Chemistry. Blackwell Science Ltd., Oxford </ref>. Phillips' research also led to the first sufficiently described enzymatic mechanism of catalytic action <ref>1967. Proc R Soc Lond B Bio 167 (1009): 389–401.</ref>. Thus, Phillips' elucidation of the function of lysozyme led Phillips to reach a more general conclusion on the diversity of enzymatic chemical action in relation to enzymatic structure. Clearly, the findings of Phillips as well as the more general historical development of the understanding of the structure and function of lysozyme have been paramount to the more general realm of enzyme chemistry.

[[Image:nag-nam2.jpg|thumb|left|350px|Lysozyme Cleavage Site]]
<ref>Image from: http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/proteins/lysozyme.htm</ref>

'''Function'''

Lysozyme is known for damaging bacterial cell walls by catalyzing the hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid (NAM) and N-acetyl-D-glucosamine (NAG) residues in peptidoglycan, and between N-acetyl-D-glucosamine residues in chitodextrins. In this way, lysozyme is efficient in lysing the cell walls of both bacteria and fungi. The location of cleavage for lysozyme on this architectural theme is the β(1-4) glycosidic linkage connecting the C1 carbon of NAM to the C4 carbon of NAG.

The particular substrate of preference for this cleavage type is a (NAG-NAM)₃ hexasaccharide, within which substrate occurs the
cleaving target glycosidic bond, NAM₄-β-O-NAG₅. The individual hexasaccharide binding units are designated A-F, with NAM₄-β-O-NAG₅ glycosidic bond cleavage preference corresponding to a D-E unit glycosidic bond cleavage preference.

= Enzymatic Activity of Lysozyme =

Enzymes are designed to attract and to bind specific substrates. The active site of and lysozyme and its specific ligands are described in the following sections

==Mechanistic Features==

'''Zymogen of Lysozyme: Enzymatic Precursor'''

Zymogens are inactive enzyme precursors. Enzymes are developed in an inactive way to prevent the enzyme from digesting the cell that produced it. This process also prevents the enzyme from becoming active in the wrong portion of the body. Lysozyme's zymogen, simply titled “pre-lysozyme,” was sequenced in 1977 by R D Palmiter, J Gagnon, L H Ericsson and K A Walsh, and has since been sequenced much more extensively.

[[Image:jrip.jpg|thumb|left|350px|Mechanism of Lysozyme]]
<ref>Image from: http://www.google.com/imgres?imgurl=http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/pics-and-strucs/lysozyme-mech.gif&imgrefurl=http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/proteins/lysozyme.htm&usg=__ormapG4XKg-tR5GrMSOdSMTV4vE=&h=603&w=801&sz=7&hl=en&start=17&zoom=1&tbnid=nvr9gvFrUILDkM:&tbnh=143&tbnw=189&prev=/images%3Fq%3DThe%2Blysozyme%2Breaction%2Bmechanism%26um%3D1%26hl%3Den%26sa%3DN%26biw%3D1280%26bih%3D647%26tbs%3Disch:10%2C304&um=1&itbs=1&iact=hc&vpx=521&vpy=349&dur=448&hovh=191&hovw=254&tx=140&ty=48&ei=JQ_LTPKzLIjCsAPkzt2KDg&oei=IA_LTP74OsG78gapm-GFAQ&esq=2&page=2&ndsp=18&ved=1t:429,r:2,s:17&biw=1280&bih=647</ref>

'''Mechanism'''

The lysozyme mechanism of action results in the hydrolysis of a glycoside (hence the familial distinction of lysozyme as a glycosylase<ref>Lysozyme, 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>), which corresponds to the conversion of an acetal to a hemiacetal, which reaction (general degradation of glycosidic bond to units "capped" by newly formed hydroxyl groups) necessitates acid catalysis, since the conversion of acetal to hemiacetal involves the protonation of the reactant oxygen prior to actual bond cleavage. <ref>Pratt, C.W., Voet, D., Voet, J.G. Fundamentals of Biochemistry - Life at the Molecular Level - Third Edition. Voet, Voet and Pratt, 2008.</ref>. Furthermore, the transition state obtained from this protonation is a covalent, oxonium ion, intermediate that must obtain resonance stabilization. The need for some means of acid catalysis and covalent resonance stabilization is adequately provided by the Glu 35 and Asp 52 residues of lysozyme, respectively. The reaction mechanism of lysozyme is demonstrated below. In the following image, the reaction begins at the upper left-hand side, and proceeds according to reaction arrows.

As seen to the left, lysozyme works by hydrolyzing the glycosidic bond, distorting the bond between the NAM and NAG. This produces a glycosyl enzyme intermediate, which reacts with a water molecule to produce the product and the unchanged enzyme.

'''Active Site'''

The <scene name='Hen_Egg-White_(HEW)_Lysozyme/Act_site/2'>active site</scene> of lysozyme is formulated as a prominent cleft outlined by the two aforementioned catalytic amino acids, Glu 35 and Asp 52. The active site is geometrically bent to augment ligand binding, and the two amino acids interact with the ligand in the binding site. Asp52 is depicted in red, and Glu35 is depicted in green.

<applet load='1hew' size='350' frame='true' align='right' caption='' />

==Binding==
'''Ligands'''

A ligand is able to bind to the active site of an enzyme to form a biologically relevant complex. The model to the right shows a space-filling model of lysozyme with the protein distinguishable in brown and the ligand distinguishable in green. Another model of the ligand can be seen in this
<scene name='Hen_Egg-White_(HEW)_Lysozyme/Ligand/1'>ribbon diagram</scene>, with the ligand protruding as a space-filling model from the active site. Here, it is clear that the ligand is a polysaccharide.

The lysozyme reaction is characterized by hydrolysis of the beta (1-4) glycosidic bond between NAM and NAG. Lysozyme has a very specific active site, which can bind only six sugar rings from a polysaccharide chain. Once lysozyme binds to this chain, it hydrolyzes them. These six sugar rings represent the ligand of lysozyme. The lysozyme then distorts the fourth sugar in the six-membered complex, producing stress on the molecule and breaking the glycosidic bond.

The amino acid side-chains Glu35 and Asp52 are critical to the activity of this enzyme. Glu35 acts as a proton donor to the glycosidic bond, cleaving the C-O bond in the substrate, and Asp52 acts as a nucleophile to generate a glycosyl enzyme intermediate. The glycosyl enzyme intermediate then reacts with a water molecule to give the product of hydrolysis.

'''Inhibitors'''

Lysozyme is best inhibited by small saccharides which act competitively with the natural substrate. The smaller saccharides will bind to the first three binding sites of the cleft (sites A-C), but will not reach sites D and E, where the enzyme cuts the glycosidic bond. So, the competitive inhibitor will stick in the cleft, not allowing the substrate to bind to the enzyme complex.<ref>http://mcdb-webarchive.mcdb.ucsb.edu/sears/biochemistry/tw-enz/lysozyme/HEWL/lysozyme-overview.htm</ref> Several known inhibitors of lysozyme are: SDS, N-acetyl-D-glucosamine, and various alcohols and oxidizing agents.<ref>http://www.worthington-biochem.com/ly/default.html</ref>

<applet load='1hew' size='350' frame='true' align='left' caption='' />

= Composition and Structure of Lysozyme =

All proteins consist of carbon, hydrogen, nitrogen, oxygen, and sulfur, as do most organic molecules. Enzymes are composed in such a way as to maximize their reactivity with their desired substrate, increasing the efficiency of biological reactions. The <scene name='Sandbox_39/Elements/1'>composition of lysozyme</scene> can be seen on the left, with the carbon atoms outlined in gray, oxygen atoms in red, nitrogen atoms in blue, sulfur atoms in yellow, and the three-letter abbreviation for the <scene name='Sandbox_39/Amino_acid_residues/1'>amino acid residues</scene> in purple.

Lysozyme, like all proteins, also contains a <scene name='Sandbox_39/C_and_n_terminal_residues/1'> 3'C and 5'N terminal </scene>, and these can be seen by following the colors of the rainbow across the molecule. Starting at the red end, the 3' C terminal end, one can work the entire way through to the 5' N terminal end, showing the folding pattern and chain of the protein.

== Secondary Structure ==

Lysozyme contains five <scene name='Sandbox_38/A/2'>alpha helical</scene> regions and five regions containing <scene name='Sandbox_38/B/1'>beta sheets</scene> as displayed in this <scene name='Sandbox_38/Alphab/1'>image</scene>. Linking these secondary structures, a number of beta turns and a large number of random coils make up the remainder of the polypeptide backbone. The polypeptide backbone of lysozyme involved in the 3 antiparallel beta sheets display the beta hairpin motif of supersecondary structure. This depiction of lysozyme contains an antiparallel beta-pleated sheet, which contributes greatly to the stability of the molecule by providing the correct alignment of hydrogen bonds. Lysozyme also contains a great deal of random coil, which is seen in the white regions of the molecule.

'''Hydrogen Bonding'''

In all proteins <scene name='Sandbox_39/Hydrogen_bonds/2'>hydrogen bonds</scene> are essential for stability. In this ribbon diagram, the hydrogen bonds can be seen between the secondary structures of lysozyme highlighted in orange. Since the double bonds of the alpha carbons in the main chain of lysozyme cause torsional strain, lysozyme is limited to very specific hydrogen bonding between the amino acid residues. This representation clearly shows how crucial hydrogen bonding is to help maintain the stability of the protein.

==Amino Acid Residues==

The amino acids present in the lysozyme polypeptide sequence have a direct influence not only on primary structure, but also on the secondary and tertiary structures, which can be influenced by polarity and charge of the sidechains. The various amino acid residues
differ in their properties because of the great variety of side chains present on each amino acid. Polar and nonpolar (and charged and uncharged) side chains lead to various degrees of hydrophobicity and hydrophilicity, which affects protein folding. In lysozyme, the <scene name='Hen_Egg-White_(HEW)_Lysozyme/Residue/1'>residues</scene> that interact with substrate are displayed.

= Bonding Interactions =

'''Disulfide Bonding in Lysozyme'''

Lysozyme contains four <scene name='Sandbox_39/Disulfide_bonds/1'>disulfide bonds</scene> involving eight cysteine residues, which are highlighted in yellow on the left. Disulfide bonds are intramolecular forces that stabilize the tertiary structure of many proteins. Disulfide bonds are present in four locations in lysozyme: between Cys 6 and Cys 127, between Cys 30 and Cys 115, between Cys 64 and Cys 80 and between Cys 76 and Cys 94.

<applet load='1hew' size='350' frame='true' align='left' caption='' />

= Intermolecular Interactions =

'''Hydrophobicity'''

Lysozyme contains both hydrophobic and hydrophilic regions ( <scene name='Sandbox_39/Hydrophobicity/2'>Hydrophobicity</scene> ). The hydrophilic effect, or the desire for proteins to be at a specific position regarding water, is the single most important determinant of protein folding. These regions can be displayed with the hydrophobic regions in gray and the polar, hydrophillic regions in purple. This coloration highlights the location of these regions, showing that the majority of the hydrophobic regions are inside of the protein and that the majority of the hydrophillic regions are on the outside of the protein.

'''Polarity'''

The nature of the amino acid sidechains in the lysozyme polypeptide sequence leads to regions of varying hydrophobicities and polarities of the enzyme structure. The presence of certain regions of hydrophilicity and hydrophobicity is a driving force in determining protein structure when folding. The varying polarities of the side chains influence the locations of residues in the enzyme structure. Nonpolar residues appear blue, and polar residues appear red in the following <scene name='Sandbox_38/Non_polar_blue/1'>polarity</scene> display of lysozyme. Nonpolar residues will display hydrophobic tendencies occurring mostly on the interior of the enzyme while polar residues will increase in abundance on the surface of the protein in order to increase contact with the aqueous solvent so as to satisfy their hydrophilic nature. By observing a space-filled structural depiction of <scene name='Sandbox_38/Non_polar_blu/1'>lysozyme polarity</scene> with polar molecules colored red and nonpolar molecules colored blue the influence of polarity on nucleotide arrangement and protein folding is evident, with the blue (nonpolar) regions inside the red (polar) regions. The presence of <scene name='Sandbox_39/Water/1'>water</scene> interacting with the various hydrophilic residues is depicted to further display how polarity affects structure. Water is depicted as yellow, and the polar and nonpolar regions remain their respective color.

'''Charge'''

Charges of the various regions of the lysozyme structure display a hydrophilic nature and thus also affect the location of that region of polypeptides and the overall folding of the protein. Charged regions of the protein will display hydrophilic tendencies and therefore will most often be located on the surface of the lysozyme molecule where they can interact with the aqueous solvent. Non-charged portions will display hydrophobic tendencies and be located on the interior of the molecule. The effect of various <scene name='Sandbox_38/Rb/1'>charges</scene> on protein structure can be visualized with charged molecules represented by red anionic and blue cationic regions, and uncharged regions colored in grey. This depiction of lysozyme uses a spacefill representation of lysozyme to depict <scene name='Sandbox_38/Chargeddd/1'>charges</scene>.

= Applications of Lysozyme =

Since lysozyme has been widely recognized for its antibacterial and antifungal properties, it has a wide variety of uses both in biochemical and pharmaceutical applications. In molecular biology, lysozyme is often used in the alkaline-lysis procedure for extracting and isolating plasmid DNA. It is used extensively in the pharmaceutical field for destroying gram-positive bacteria, and can be used to support already-existing immune defenses to fight bacterial infections. This enzyme is particularly important for preventing bacterial diseases in infants. Because of its antibacterial properties, lysozyme can also be used in the food industry to help prevent spoilage of foods.

= Discovery and Applications of Hen Egg-White Lysozyme=

<applet load='aln_1H6M_to_1HEW_2.pdb' size='300' frame='true' align='right' caption=' Hen Egg White (HEW) Lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to the active site, PDBid 1HEW' scene='User:Judy_Voet/Lysozyme/Lysozyme1/16' />
Lysozyme was the first enzyme whose X-ray structure was determined <ref> PMID 5840126</ref><ref>Phillips, D. C. The hen egg white lysozyme molecule. Proc. Natl Acad. Sci. USA 57, 483-495 (1967)</ref>. This <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>scene </scene> shows Hen Egg White (HEW) lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to a cleft in the enzyme. David Phillips, who determined the structure in 1965, saw that the cleft was large enough to fit three more saccharide units.
He therefore built a model extending the trisaccharide to a
<scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> that fits into the cleft, labeling the sugar subsites A-F<ref> coordinates of the model kindly provided by Louise Johnson</ref>. Alternately click on <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>trisaccharide</scene> and <scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> to turn the modeled portion of the hexasaccharide on and off.

The interesting thing about the model was that the only way that the hexasaccharide would fit into the cleft was if the 4th saccharide (in subsite D) was strained into a <scene name='User:Judy_Voet/Lysozyme/Half-chair/2'>half-chair conformation</scene>. This conformation is what would be necessary for the formation of an oxocarbenium ion (oxionium ion). When the model was studied, <scene name='User:Judy_Voet/Lysozyme/Glu_35/1'>Glu 35</scene> was found to be in an ideal location to act as a general acid catalyst, 3.34 Angstroms from the bridging oxygen between the 4th and 5th saccharide units. <scene name='User:Judy_Voet/Lysozyme/Asp_52/2'>Asp 52</scene> appeared to be too far away (2.69 angstroms) in the static lysozyme structure to have formed a covalent bond with C1 of the half-chair model in the D site, and no covalent intermediate had ever been detected, so Phillips proposed that it acted as an electrostatic stabilizer of the oxonium ion (referred to as The Phillips Mechanism).

<applet load='aln_1H6M_to_1HEW_2.pdb' size='200' frame='true' align='left' caption='NAG-2-deoxy-2-fluoro-glucosyl fluoride (NAG2FGlcF) bound to Glu35Gln HEW Lysozyme PDBid 1H6M' scene='User:Judy_Voet/Lysozyme/1h6m/3'/>

Then, in 2001, Stephen Withers published <scene name='User:Judy_Voet/Lysozyme/1h6m/3'>1H6M</scene>,<ref>PMID 11518970</ref> in which Glu 35 had been mutated to Gln to remove the general acid catalyst. The substrate contained NAG-2-fluoro-glucosyl fluoride (NAG2FGlcF). The fluoro group on C-1 does not require acid catalysis to be a good leaving group, and the remaining saccharide, in the absence of the acid necessary to catalyse the second step of the reaction, was demonstrated to form a <scene name='User:Judy_Voet/Lysozyme/Covalent/1'> covalent intermediate</scene>. In this <scene name='User:Judy_Voet/Lysozyme/Superposition/2'>superposition</scene> of the half chair model with 1HEW (greens) and the covalent intermediate in 1H6M (blues), note the relatively small motions of Asp 52 and C1 of the sugar ring in going from the model to the covalent intermediate. to observe the motion from the <scene name='User:Judy_Voet/Lysozyme/Asp52_halfchair/1'>half-chair</scene> to the <scene name='User:Judy_Voet/Lysozyme/Covalent/2'>covalent intermediate</scene> just toggle between the two green links.

== 3D Structures of Lysozyme ==

===Lys===

[[2x0a]], [[3iju]], [[3ijv]], [[3a8z]], [[2w1y]], [[2w1m]], [[2w1x]], [[2w1l]], [[3e3d]], [[3exd]], [[2zq3]], [[2zq4]], [[3b72]], [[3b6l]], [[2z12]], [[2z18]], [[2z19]], [[2vb1]], [[2hu3]], [[2hub]], [[2htx]], [[2hu1]], [[2yvb]], [[2epe]], [[2g4p]], [[2g4q]], [[2cgi]], [[2b5z]], [[2d4k]], [[2d91]], [[2f2n]], [[2fbb]], [[2c8o]], [[2c8p]], [[2a6u]], [[2aub]], [[2blx]], [[2bly]], [[2a7d]], [[2a7f]], [[1wtm]], [[1wtn]], [[1w6z]], [[1vdp]], [[1vdq]], [[1vds]], [[1vdt]], [[1ved]], [[1v7t]], [[1ps5]], [[2cds]], [[1lj3]], [[1lj4]], [[1lje]], [[1ljf]], [[1ljg]], [[1ljh]], [[1lji]], [[1ljj]], [[1ljk]], [[1jis]], [[1jit]], [[1jiy]], [[1jj0]], [[1jj1]], [[1jj3]], [[1iee]], [[1qio]], [[1f0w]], [[1f10]], [[1dpx]], [[1c10]], [[1qtk]], [[1lz8]], [[1lz9]], [[1bhz]], [[1bgi]], [[1bwh]], [[1bwi]], [[1bwj]], [[1bvx]], [[1hsw]], [[1hsx]], [[1lpi]], [[4lzt]], [[3lzt]], [[1aki]], [[1jpo]], [[1rfp]], [[193l]], [[194l]], [[5lym]], [[1lza]], [[3lyt]], [[4lyt]], [[5lyt]], [[6lyt]], [[2lzt]], [[1lzt]], [[1lzh]], [[2lzh]], [[7lyz]], [[1lyz]], [[2lyz]], [[3lyz]], [[4lyz]], [[5lyz]], [[6lyz]] - HEWL – chicken 
[[1xei]], [[1xej]], [[1xek]], [[1uco]], [[1lma]], [[4lym]] – HEWL low hydration 
[[1lsa]], [[1lsb]], [[1lsc]], [[1lsd]], [[1lse]], [[1lsf]], [[1lys]] – HEWL temperature influence 
[[2lym]], [[3lym]] – HEWL pressure influence 
[[132l]] – HEWL methylated 
[[1rcm]] – HEWL 3 S-S form 
[[2xbr]], [[2xbs]]- HEWL– Raman crystallography 
[[2zwb]], [[1io5]], [[1lzn]] - HEWL– Neutron 
[[1gxv]], [[1gxx]], [[1e8l]] - HEWL- NMR 
[[2hs7]], [[2hso]], [[2hs9]]- HEWL– Powder diffraction 
[[1ir7]], [[1ir8]], [[1ir9]], [[1ioq]], [[1ior]], [[1ios]], [[1iot]], [[1flq]], [[1flu]], [[1flw]], [[1fly]], [[1fn5]], [[1kxw]], [[1kxx]], [[1kxy]], [[1uia]], [[1uib]], [[1uic]], [[1uid]], [[1uie]], [[1uif]], [[1uig]], [[1uih]], [[1lsm]], [[1lsn]], [[1hel]], [[1hem]], [[1hen]], [[1heo]], [[1hep]], [[1heq]], [[1her]] – HEWL (mutant) 
[[1lyo]], [[2lyo]], [[3lyo]], [[4lyo]] – HEWL cross-linked 
[[1xft]] - tuLys – turkey - Powder diffraction 
[[1jse]], [[1tew]], [[135l]], [[2lz2]], [[1lz2]] – tuLys 
[[3lz2]] – tuLys - Laue 
[[3ab6]] – Lys + NAG3 – Hard clam 
[[2x8r]] – Lys GH25 – ''Aspergillus fumigatus'' 
[[3mgw]] – Lys G – Atlantic salmon 
[[3gxk]], [[3gxr]] – Lys G + NAG – Atlantic cod 
[[2fbd]] – HfLys 1 
[[3cb7]] – HfLys 2 
[[2zij]], [[2zik]], [[2zil]], [[2nwd]], [[1iwt]], [[1iwu]], [[1iwv]], [[1iww]], [[1iwx]], [[1iwy]], [[1iwz]], [[1jwr]], [[1jsf]], [[1rex]], [[1lz1]] – hLys – human 
[[1w08]], [[1ix0]], [[1ioc]], [[1ip1]], [[1ip2]], [[1ip3]], [[1ip4]], [[1ip5]], [[1ip6]], [[1ip7]], [[1qsw]], [[1gev]], [[1gez]], [[1gf0]], [[1gf3]], [[1gf4]], [[1gf5]], [[1gf6]], [[1gf7]], [[1i1z]], [[1i20]], [[1i22]], [[1gfr]], [[1gft]], [[1gfu]], [[1gfv]], [[1gf8]], [[1gf9]], [[1gfa]], [[1gfe]], [[1gfg]], [[1gfh]], [[1gfj]], [[1gfk]], [[1inu]], [[1gdx]], [[1ge0]], [[1ge1]], [[1ge2]], [[1ge3]], [[1ge4]], [[1gdw]], [[1gaz]], [[1gb0]], [[1gb2]], [[1gb3]], [[1gb5]], [[1gb6]], [[1gb7]], [[1gb8]], [[1gb9]], [[1gbo]], [[1gbw]], [[1gbx]], [[1gby]], [[1gbz]], [[1gay]], [[1eq4]], [[1eq5]], [[1eqe]], [[1c7p]], [[1di3]], [[1di4]], [[1di5]], [[1c43]], [[1c45]], [[1c46]], [[1ckg]], [[1cj6]], [[1cj7]], [[1cj8]], [[1cj9]], [[1ckc]], [[1ckd]], [[1ckf]], [[1ckh]], [[1b5z]], [[1b70]], [[1b7q]], [[1b7r]], [[1b7s]], [[1b7l]], [[1b7m]], [[1b7n]], [[1b7p]], [[1b5u]], [[1b5v]], [[1b5w]], [[1b5x]], [[1b5y]], [[1bb3]], [[1bb4]], [[2bqa]], [[2bqb]], [[2bqc]], [[2bqd]], [[2bqe]], [[2bqf]], [[2bqg]], [[2bqh]], [[2bqi]], [[2bqj]], [[2bqk]], [[2bql]], [[2bqm]], [[2bqn]], [[2bqo]], [[2mea]], [[2meb]], [[2mec]], [[2med]], [[2mee]], [[2mef]], [[2meg]], [[2meh]], [[2mei]], [[1wqm]], [[1wqn]], [[1wqo]], [[1wqp]], [[1wqq]], [[1wqr]], [[2heb]], [[2hea]], [[2hec]], [[2hed]], [[2hee]], [[2hef]], [[1jka]], [[1jkb]], [[1jkc]], [[1jkd]], [[1loz]], [[1lyy]], [[1oua]], [[1oub]], [[1ouc]], [[1oud]], [[1oue]], [[1ouf]], [[1oug]], [[1ouh]], [[1oui]], [[1ouj]], [[207l]], [[208l ]], [[1yam]], [[1yan]], [[1yao]], [[1yap]], [[1yaq]], [[1lmt]], [[1lhh]], [[1lhi]], [[1lhj]], [[1lhk]], [[1lhl]], [[133l]], [[134l]], [[1lz4]], [[1lz5]], [[1lz6]], [[1laa]], [[1tay]], [[1tby]], [[1tcy]], [[1tdy]], [[2lhm]], [[3lhm]] – hLys (mutant) 
[[1iy3]], [[1iy4]] – hLys - NMR 
[[2z2f]] – Lys – Bovine 
[[2cwi]], [[1el1]], [[1qqy]] – dLys - dog 
[[2z2e]] – dLys (mutant) 
[[1i56]] – dLys – NMR 
[[2dqa]] – Lys – ''Tapes japonica'' 
[[2gv0]] – Lys – Soft-shelled turtle 
[[1ivm]] – mLys M – NMR – mouse 
[[1jfx]] – Lys – ''Streptomyces coelicolor'' 
[[1gd6]] – Lys – ''Bombyx mori'' 
[[1jug]] – Lys – Echidna 
[[1dkj]] – BqLys – Bobwhite quail 
[[2ihl]] – Lys – Japanese quail 
[[1gbs]] – BsLys – Black swan 
[[1lmn]] – RtLys – Rainbow trout 
[[2eql]] – Lys – horse 
[[1ghl]] – phLys – pheasant 
[[1hhl]] – GfLys – Guinea fowl 
[[1lhm]] – Lys (mutant) – yeast 

===Lys small molecules complexes===

[[3fe0]], [[2d4i]], [[2d4j]], [[1v7s]] - HEWL+ D2O 
[[3m3u]] – HEWL Trp fluorescence 
[[2xjw]] - HEWL + CO 
[[1hf4]], [[1lks]] – HEWL + NO3 
[[3a34]], [[3ems]] - HEWL + arginine 
[[2xth]] – cLys + inhibitor K2PtBr6 
[[3a90]], [[3a91]], [[3a92]], [[3a93]], [[3a94]], [[3a95]], [[3a96]], [[3kam]], [[2pc2]], [[2bpu]], [[1t3p]], [[1h87]] – HEWL + rare earth 
[[2d6b]], [[2hg0]], [[1vat]], [[1gwd]], [[1b2k]], [[1lkr]], [[1azf]], [[8lyz]]- HEWL+ halogen 
[[1vat]] - HEWL + Xe 
[[1n4f]] - HEWL + As 
[[2i6z]] - HEWL + Pt drug 
[[2zyp]] - HEWL + poly (allyl amine) 
[[2f30]], [[2f4a]] – HEWL + urea derivative 
[[2f4g]], [[1ykx]], [[1yky]], [[1ykz]], [[1yl0]], [[1yl1]], [[1z55]] - HEWL + alcohol 
[[1dpw]] – HEWL + MPD 
[[1lcn]] – HEWL + SCN 
[[2zxs]] - HEWL with glycine-amide 
[[2h9j]], [[2h9k]], [[1yik]], [[1yil]] - HEWL + cyclam derivative 
[[1b0d]] – HEWL + p-toluene-sulfonate 
[[2q0m]] - HEWL + tricarbonylmanganese 
[[2war]] – HEWL (mutant) + chitopentaose 
[[2h5z]] – HfLys 1 + chitotetraose – House fly 
[[1hnl]] – hLys + glutathione 
[[1dkk]] – BqLys + NO3 

===Lys complex with glucoside===

[[3a3q]] – HEWL (mutant) + NAG 
[[1sf4]], [[1sf6]], [[1sf7]], [[1sfb]], [[1sfg]], [[1ja2]], [[1ja4]], [[1ja6]], [[1ja7]] – HEWL + NAG oligosaccharide – Powder diffraction 
[[1ubz]], [[1d6p]], [[1d6q]], [[1bb5]] – hLys (mutant) + glycoside 
[[1uc0]], [[1re2]], [[1rem]], [[1rey]], [[1rez]], [[1lzr]], [[1lzs]] - hLys + glycoside 
[[1ljn]], [[1jef]], [[1lzy]] – tuLys + glycoside 
[[1h6m]], [[1at5]], [[1at6]], [[1lzb]], [[1lzc]], [[1lzd]], [[1lze]], [[1lzg]], [[1hew ]]– HEWL + glycoside 
[[1lsy]], [[1lsz]] - HEWL (mutant) + glycoside 
[[1bb6]], [[1bb7]] – RtLys + glycoside 
[[1lmc]] – RtLys + bulgecin 
[[1lmo]], [[1lmp]], [[1lmq]] – RtLys + glucoside 
[[1lsp]] – BsLys + bulgecin 
[[153l]], [[154l]] – Lys +glucoside – goose 

===Phage Lys===

[[2oe4]], [[2oe7]], [[2oe9]], [[2oea]], [[1swz]], [[1cx6]], [[1qtc]], [[1qtd]], [[1qth]], [[1qsb]], [[1qs5]], [[1qs9]], [[1qtb]], [[256l]], [[206l]], [[167l]], [[168l]], [[169l]], [[170l]], [[171l]], [[172l]], [[173l]], [[174l]], [[175l]], [[176l]], [[177l]], [[178l]], [[181l]], [[182l]], [[183l]], [[184l]], [[185l]], [[186l]], [[187l]], [[188l]], [[1nhb]], [[137l]], [[216l]], [[152l]], [[149l]], [[150l]], [[151l]], [[1lyd]], [[2lzm]] - T4Lys – Enterobacteria phage T4 
[[138l]] – T4Lys cross-linked 
[[4lzm]], [[5lzm]], [[6lzm]], [[7lzm]] – T4Lys ionic strength 
[[3l2x]], [[3k2r]], [[3g3v]], [[3g3w]], [[3g3x]], [[2q9d]], [[2q9e]], [[2igc]], [[2ntg]], [[2nth]], [[2ou8]], [[2ou9]], [[1zur]], [[1zwn]], [[1zyt]], [[2cuu]], [[2a4t]] – T4Lys (mutant) spin labeled 
[[3l64]], [[3hwl]], [[3jr6]], [[3gui]], [[3c7w]], [[3c7y]], [[3c7z]], [[3c80]], [[3c81]], [[3c82]], [[3c83]], [[3c8q]], [[3c8r]], [[3c8s]], [[3cdo]], [[3cdq]], [[3cdr]], [[3cdt]], [[3cdv]], [[3f8v]], [[3f9l]], [[3fa0]], [[3fad]], [[3fi5]], [[3dke]], [[3dmv]], [[2o4w]], [[2o79]], [[2o7a]], [[2huk]], [[2hul]], [[2hum]], [[2b7x]], [[2b6t]], [[2b6w]], [[2b6x]], [[2b6y]], [[2b6z]], [[2b70]], [[2b72]], [[2b73]], [[2b74]], [[2b75]], [[1sx7]], [[1swy]], [[1sx2]], [[1t6h]], [[1ssw]], [[1ssy]], [[1t8f]], [[1t8g]], [[1t8a]], [[1t97]], [[1p56]], [[1p5c]], [[1p2l]], [[1p2r]], [[1p36]], [[1p37]], [[1p3n]], [[1p46]], [[1p64]], [[1p6y]], [[1p7s]], [[1pqd]], [[1pqi]], [[1pqj]], [[1pqk]], [[1pqm]], [[1pqo]], [[1oyu]], [[1ks3]], [[1kw5]], [[1kw7]], [[1ky0]], [[1ky1]], [[1l0j]], [[1l0k]], [[1lw9]], [[1lwg]], [[1lwk]], [[1lpy]], [[1llh]], [[1lgu]], [[1li6]], [[1jtm]], [[1jtn]], [[1jqu]], [[1kni]], [[1g06]], [[1g07]], [[1g0g]], [[1g0j]], [[1g0k]], [[1g0l]], [[1g0m]], [[1g0p]], [[1g0q]], [[1g1v]], [[1g1w]], [[1i6s]], [[257l]], [[258l]], [[260l]], [[1epy]], [[1b6i]], [[1cu6]], [[1d9w]], [[1ctw]], [[1cu0]], [[1cu2]], [[1cu3]], [[1cu5]], [[1cv1]], [[1cv4]], [[1cv5]], [[1cv6]], [[1cvk]], [[1cx7]], [[1d2w]], [[1d2y]], [[1d3f]], [[1d3j]], [[1d3m]], [[1d3n]], [[1cv3]], [[1qt3]], [[1qt4]], [[1qt5]], [[1qt6]], [[1qt7]], [[1qt8]], [[1qtv]], [[1qtz]], [[1qud]], [[1qug]], [[1quh]], [[1quo]], [[1qsq]], [[261l]], [[262l]], [[259l]], [[220l]], [[222l]], [[223l]], [[225l]], [[226l]], [[227l]], [[228l]], [[229l]], [[235l]], [[236l]], [[237l]], [[238l]], [[239l]], [[240l]], [[241l]], [[242l]], [[243l]], [[244l]], [[245l]], [[246l]], [[247l]], [[248l]], [[249l]], [[250l]], [[251l]], [[252l]], [[253l]], [[254l]], [[255l]], [[230l]], [[231l]], [[232l]], [[233l]], [[234l]], [[209l]], [[210l]], [[211l]], [[212l]], [[213l]], [[214l]], [[215l]], [[218l]], [[219l]], [[180l]], [[195l]], [[196l]], [[197l]], [[198l]], [[199l]], [[200l]], [[190l]], [[191l]], [[192l]], [[189l]], [[155l]], [[156l]], [[157l]], [[158l]], [[159l]], [[160l]], [[161l]], [[162l]], [[163l]], [[164l]], [[165l]], [[166l]], [[129l]], [[130l]], [[131l]], [[140l]], [[141l]], [[142l]], [[143l]], [[144l]], [[145l]], [[146l]], [[147l]], [[201l]], [[205l]], [[221l]], [[224l]], [[102l]], [[103l]], [[104l]], [[107l]], [[108l]], [[109l]], [[110l]], [[111l]], [[112l]], [[113l]], [[114l]], [[115l]], [[118l]], [[119l]], [[120l]], [[122l]], [[123l]], [[125l]], [[126l]], [[127l]], [[128l]], [[1dya]], [[1dyb]], [[1dyc]], [[1dyd]], [[1dye]], [[1dyf]], [[1dyg]], [[1l00]], [[1l85]], [[1l86]], [[1l87]], [[1l88]], [[1l89]], [[1l90]], [[1l91]], [[1l92]], [[1l93]], [[1l94]], [[1l95]], [[1l96]], [[1l97]], [[1l98]], [[1l99]], [[1lye]], [[1lyf]], [[1lyg]], [[1lyh]], [[1lyi]], [[1lyj]], [[217l]], [[1tla]], [[1l77]], [[1l79]], [[1l80]], [[1l81]], [[1l82]], [[2l78]], [[1l36]], [[1l37]], [[1l38]], [[1l39]], [[1l40]], [[1l41]], [[1l42]], [[1l43]], [[1l44]], [[1l45]], [[1l46]], [[1l47]], [[1l48]], [[1l49]], [[1l50]], [[1l51]], [[1l52]], [[1l53]], [[1l54]], [[1l55]], [[1l56]], [[1l57]], [[1l58]], [[1l59]], [[1l60]], [[1l61]], [[1l62]], [[1l63]], [[1l64]], [[1l65]], [[1l66]], [[1l67]], [[1l68]], [[1l69]], [[1l70]], [[1l71]], [[1l72]], [[1l73]], [[1l74]], [[1l75]], [[1l76]], [[1l17]], [[1l18]], [[1l19]], [[1l20]], [[1l21]], [[1l22]], [[1l23]], [[1l24]], [[1l25]], [[1l26]], [[1l27]], [[1l28]], [[1l29]], [[1l30]], [[1l31]], [[1l32]], [[1l33]], [[1l34]], [[1l35]], [[3lzm]], [[1l01]], [[1l02]], [[1l03]], [[1l04]], [[1l05]], [[1l06]], [[1l07]], [[1l08]], [[1l09]], [[1l10]], [[1l11]], [[1l12]], [[1l13]], [[1l14]], [[1l15]], [[1l16]] – T4Lys (mutant) 
[[1c60]], [[1c61]], [[1c62]], [[1c63]], [[1c64]], [[1c65]], [[1c66]], [[1c67]], [[1c68]], [[1c69]], [[1c6a]], [[1c6b]], [[1c6c]], [[1c6d]], [[1c6e]], [[1c6f]], [[1c6g]], [[1c6h]], [[1c6i]], [[1c6j]], [[1c6k]], [[1c6l]], [[1c6m]], [[1c6n]], [[1c6p]], [[1c6q]], [[1c6t]] - T4Lys (mutant) + noble gas 
[[3ht6]], [[3ht7]], [[3ht8]], [[3ht9]], [[3htb]], [[3hu8]], [[3huq]], [[3guj]], [[3guk]], [[3gul]], [[3gum]], [[3gun]], [[3guo]], [[3gup]], [[3dmx]], [[3dmz]], [[3dn0]], [[3dn1]], [[3dn2]], [[3dn3]], [[3dn4]], [[3dn6]], [[3dn8]], [[3dna]], [[2rb1]], [[2ray]], [[2raz]], [[2rb0]], [[2rb2]], [[2rbn]], [[2rbo]], [[2rbq]], [[2rbr]], [[2rbs]], [[2oty]],[[2otz]], [[1owy]], [[1owz]], [[1ov5]], [[1ov7]], [[1ovh]], [[1ovj]], [[1ovk]], [[1lgw]], [[1lgx]], [[1li2]], [[1li3]], [[1l83]], [[1l84]] – T4Lys (mutant) + benzene derivative 
[[3htd]], [[3htf]], [[3htg]], [[3hu9]], [[3hua]], [[3huk]], [[3hh3]], [[3hh4]], [[3hh5]], [[3hh6]], [[2rbp]], [[2ou0]], [[2f2q]], [[2f32]], [[2f47]], [[1xep]] – T4Lys (mutant) + inhibitor 
[[148l]] - T4Lys (mutant) + glucoside 
[[3d3d]], [[1d9u]] – lamLys + chitohexasaccharide 
[[1am7]] – lamLys - Enterobacteria phage λ 
[[2anv]], [[2anx]] – Lys (mutant)]] - Enterobacteria phage p22 
[[1xjt]], [[1xju]] - Lys - Enterobacteria phage p1 
[[1lba]] - T7Lys - Enterobacteria phage T7 

===Lys protein complex===

[[3m18]], [[3g3a]], [[3g3b]] - HEWL + Variable lymphocyte receptor – Marine lamprey 
[[3a67]], [[3a6b]], [[3a6c]], [[2yss]], [[2eiz]], [[2dqc]], [[2dqd]], [[2dqe]], [[2dqf]], [[2dqg]], [[2dqh]], [[2dqi]], [[2dqj]], [[1j1o]], [[1j1p]], [[1j1x]], [[1ic4]], [[1ic5]], [[1ic7]] – HEWL + mLys antibody HYHEL-10 (mutant) 
[[1xgp]], [[1xgq]], [[1xgr]], [[1xgt]], [[1xgu]] – HEWL + mLys antibody HYHEL-63 
[[3d9a]], [[2eks]], [[1ua6]], [[1c08]], [[3hfm]] – HEWL + mLys antibody HYHEL-10 
[[1uac]] - tuLys C + mLys antibody HYHEL-10 
[[1yqv]], [[2iff]] – HEWL + mLys antibody HYHEL-5 
[[1bql]] – BqLys + mLys antibody HYHEL-5 
[[1ndg]] – HEWL + mLys antibody HYHEL-8 
[[1ndm]] – HEWL + mLys antibody HYHEL-26 
[[1dqj]] - HEWL + mLys antibody HYHEL-63 
[[1nby]], [[1nbz]] – HEWL (mutant) + mLys antibody HYHEL-63 
[[1g7h]], [[1g7i]], [[1g7j]], [[1g7l]], [[1g7m]], [[1kip]], [[1kiq]], [[1kir]] – HEWL + mAnti-HEWL monoclonal antibody (mutant) 
[[1mlc]], [[1vfb]] - HEWL + mIGG1-κ D44.1 FAB 
[[1a2y]] - HEWL (mutant) + mIGG1-κ D1.3 FV 
[[1fdl]] - HEWL + mIGG1-κ D1.3 FAB 
[[1jhl]] – phLys + mIGG1-κ D11.15 FV 
[[1fbi]] – GfLys + mIGG1 F9.13.7 FAB 
[[2znw]], [[2znx]] – HEWL + hSCFV10 antibody 
[[1bvk]] - HEWL + hAnti Lys FV antibody 
[[1dzb]] – tuLys + mSCFV 1F9 
[[1zv5]], [[1zvh]], [[1zvy]], [[1zmy]], [[1ri8]], [[1rjc]], [[1xfp]], [[1jtp]], [[1jtt]], [[1jto]], [[1mel]] - HEWL + cAntibody heavy chain domain – camel 
[[1op9]] - hLys C + cAntibody heavy chain domain 
[[3otp]] – HEWL + EcProtease DO – ''Escherichia coli'' 
[[3f6z]] - HEWL + MLIC – ''Pseudomonas aeruginosa'' 
[[3eba]] – hLys C + hCABHUL6 
[[2qb0]], [[2qar]] – T4Lys/E80 TELSAM domain 
[[2i25]], [[2i26]] - HEWL +NsAntigen receptor PBLA8 variable domain – Nurse shark 
[[1sq2]], [[1t6v]] – HEWL +NsNew Antigen receptor variable domain 
[[1gpq]] – HEWL + EcInhibitor of Vertebrate Lys 
[[1aro]] – T7Lys + T7 RNA polymerase 

===Some Useful External Links===
[http://en.wikipedia.org/wiki/Lysozyme Lysozyme]

[http://en.wikipedia.org/wiki/Glycoside_hydrolase#Retaining_glycoside_hydrolases Retaining Glycoside Hydrolases]

===References===
<references/>

Hen Egg-White (HEW) Lysozyme

2011-04-20T18:33:39Z

Anne Goodling:

'''Introduction'''

Lysozyme - also known as muramidase, or glycoside hydrolase - is a powerful enzyme of biological significance found in abundance in tears, saliva, and human milk. In humans, it is encoded in the ''LYZ'' gene. Although it is responsible for the initial digestion of starches in the mouth, it is most widely identified as a non-specific defense in gram positive bacteria and in many species of fungi. Due to its antibacterial effects, it is a strong component of the innate immune system, and is an important part of an infant's diet to ward off diarrheal diseases. Since it is a small, easily available, and highly stable protein containing only 129 amino acid residues, it has been subject to extensive research regarding its function and structure. Hen Egg White (HEW) Lysozyme is shown below.

===History===

Lysozyme is an enzyme known for its unique ability to degrade the polysaccharide architecture of many kinds of cell walls, normally for the purpose of protection against bacterial infection<ref>Lysozyme. 2010. Citizendium.org. http://en.citizendium.org/wiki/Lysozyme</ref>. Its effects were first noticed by Laschtschenko in 1909. It was officially characterized and termed “lysozyme” by Alexander Fleming, the same person credited for the accidental discovery of penicillin.
The characterization of lysozyme in 1922 by Alexander Fleming was providential in that the undertaken experiment related to the discovery of lysozyme was not geared toward any knowledge of such a protein as lysozyme <ref>Lysozyme. 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>. During the unrelated experiment, nasal drippings were inadvertently introduced to a petri dish containing a bacterial culture, which culture consequently exhibited the results of an as yet unknown enzymatic reaction. The observation of this unknown reaction led to further research on the components of this reaction as well as to the corresponding identification of the newfound "lysozyme." Fleming's discovery was complemented by David C. Phillips' 1965 description of the three-dimensional structure of lysozyme via a 200 pm resolution model obtained from X-ray crystallography <ref>Lysozyme, 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>. Phillips' work was especially groundbreaking since Phillips had managed to successfully elucidate the structure of an enzyme via X-ray crystallography - a feat that had never before been accomplished<ref>Bugg, T. 1997. An Introduction to Enzyme and Coenzyme Chemistry. Blackwell Science Ltd., Oxford </ref>. Phillips' research also led to the first sufficiently described enzymatic mechanism of catalytic action <ref>1967. Proc R Soc Lond B Bio 167 (1009): 389–401.</ref>. Thus, Phillips' elucidation of the function of lysozyme led Phillips to reach a more general conclusion on the diversity of enzymatic chemical action in relation to enzymatic structure. Clearly, the findings of Phillips as well as the more general historical development of the understanding of the structure and function of lysozyme have been paramount to the more general realm of enzyme chemistry.

[[Image:nag-nam2.jpg|thumb|left|350px|Lysozyme Cleavage Site]]
<ref>Image from: http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/proteins/lysozyme.htm</ref>

'''Function'''

Lysozyme is known for damaging bacterial cell walls by catalyzing the hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid (NAM) and N-acetyl-D-glucosamine (NAG) residues in peptidoglycan, and between N-acetyl-D-glucosamine residues in chitodextrins. In this way, lysozyme is efficient in lysing the cell walls of both bacteria and fungi. The location of cleavage for lysozyme on this architectural theme is the β(1-4) glycosidic linkage connecting the C1 carbon of NAM to the C4 carbon of NAG.

The particular substrate of preference for this cleavage type is a (NAG-NAM)₃ hexasaccharide, within which substrate occurs the
cleaving target glycosidic bond, NAM₄-β-O-NAG₅. The individual hexasaccharide binding units are designated A-F, with NAM₄-β-O-NAG₅ glycosidic bond cleavage preference corresponding to a D-E unit glycosidic bond cleavage preference.

= Enzymatic Activity of Lysozyme =

Enzymes are designed to attract and to bind specific substrates. The active site of and lysozyme and its specific ligands are described in the following sections

==Mechanistic Features==

'''Zymogen of Lysozyme: Enzymatic Precursor'''

Zymogens are inactive enzyme precursors. Enzymes are developed in an inactive way to prevent the enzyme from digesting the cell that produced it. This process also prevents the enzyme from becoming active in the wrong portion of the body. Lysozyme's zymogen, simply titled “pre-lysozyme,” was sequenced in 1977 by R D Palmiter, J Gagnon, L H Ericsson and K A Walsh, and has since been sequenced much more extensively.

[[Image:jrip.jpg|thumb|left|350px|Mechanism of Lysozyme]]
<ref>Image from: http://www.google.com/imgres?imgurl=http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/pics-and-strucs/lysozyme-mech.gif&imgrefurl=http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/proteins/lysozyme.htm&usg=__ormapG4XKg-tR5GrMSOdSMTV4vE=&h=603&w=801&sz=7&hl=en&start=17&zoom=1&tbnid=nvr9gvFrUILDkM:&tbnh=143&tbnw=189&prev=/images%3Fq%3DThe%2Blysozyme%2Breaction%2Bmechanism%26um%3D1%26hl%3Den%26sa%3DN%26biw%3D1280%26bih%3D647%26tbs%3Disch:10%2C304&um=1&itbs=1&iact=hc&vpx=521&vpy=349&dur=448&hovh=191&hovw=254&tx=140&ty=48&ei=JQ_LTPKzLIjCsAPkzt2KDg&oei=IA_LTP74OsG78gapm-GFAQ&esq=2&page=2&ndsp=18&ved=1t:429,r:2,s:17&biw=1280&bih=647</ref>

'''Mechanism'''

The lysozyme mechanism of action results in the hydrolysis of a glycoside (hence the familial distinction of lysozyme as a glycosylase<ref>Lysozyme, 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>), which corresponds to the conversion of an acetal to a hemiacetal, which reaction (general degradation of glycosidic bond to units "capped" by newly formed hydroxyl groups) necessitates acid catalysis, since the conversion of acetal to hemiacetal involves the protonation of the reactant oxygen prior to actual bond cleavage. <ref>Pratt, C.W., Voet, D., Voet, J.G. Fundamentals of Biochemistry - Life at the Molecular Level - Third Edition. Voet, Voet and Pratt, 2008.</ref>. Furthermore, the transition state obtained from this protonation is a covalent, oxonium ion, intermediate that must obtain resonance stabilization. The need for some means of acid catalysis and covalent resonance stabilization is adequately provided by the Glu 35 and Asp 52 residues of lysozyme, respectively. The reaction mechanism of lysozyme is demonstrated below. In the following image, the reaction begins at the upper left-hand side, and proceeds according to reaction arrows.

As seen to the left, lysozyme works by hydrolyzing the glycosidic bond, distorting the bond between the NAM and NAG. This produces a glycosyl enzyme intermediate, which reacts with a water molecule to produce the product and the unchanged enzyme.

'''Active Site'''

The <scene name='Hen_Egg-White_(HEW)_Lysozyme/Act_site/2'>active site</scene> of lysozyme is formulated as a prominent cleft outlined by the two aforementioned catalytic amino acids, Glu 35 and Asp 52. The active site is geometrically bent to augment ligand binding, and the two amino acids interact with the ligand in the binding site. Asp52 is depicted in red, and Glu35 is depicted in green.

<applet load='1hew' size='350' frame='true' align='right' caption='' />

==Binding==
'''Ligands'''

A ligand is able to bind to the active site of an enzyme to form a biologically relevant complex. The model to the right shows a space-filling model of lysozyme with the protein distinguishable in brown and the ligand distinguishable in green. Another model of the ligand can be seen in this
<scene name='Hen_Egg-White_(HEW)_Lysozyme/Ligand/1'>ribbon diagram</scene>, with the ligand protruding as a space-filling model from the active site. Here, it is clear that the ligand is a polysaccharide.

The lysozyme reaction is characterized by hydrolysis of the beta (1-4) glycosidic bond between NAM and NAG. Lysozyme has a very specific active site, which can bind only six sugar rings from a polysaccharide chain. Once lysozyme binds to this chain, it hydrolyzes them. These six sugar rings represent the ligand of lysozyme. The lysozyme then distorts the fourth sugar in the six-membered complex, producing stress on the molecule and breaking the glycosidic bond.

The amino acid side-chains Glu35 and Asp52 are critical to the activity of this enzyme. Glu35 acts as a proton donor to the glycosidic bond, cleaving the C-O bond in the substrate, and Asp52 acts as a nucleophile to generate a glycosyl enzyme intermediate. The glycosyl enzyme intermediate then reacts with a water molecule to give the product of hydrolysis.

'''Inhibitors'''

Lysozyme is best inhibited by small saccharides which act competitively with the natural substrate. The smaller saccharides will bind to the first three binding sites of the cleft (sites A-C), but will not reach sites D and E, where the enzyme cuts the glycosidic bond. So, the competitive inhibitor will stick in the cleft, not allowing the substrate to bind to the enzyme complex.<ref>http://mcdb-webarchive.mcdb.ucsb.edu/sears/biochemistry/tw-enz/lysozyme/HEWL/lysozyme-overview.htm</ref> Several known inhibitors of lysozyme are: SDS, N-acetyl-D-glucosamine, and various alcohols and oxidizing agents.<ref>http://www.worthington-biochem.com/ly/default.html</ref>

<applet load='1hew' size='350' frame='true' align='left' caption='' />

= Composition and Structure of Lysozyme =

All proteins consist of carbon, hydrogen, nitrogen, oxygen, and sulfur, as do most organic molecules. Enzymes are composed in such a way as to maximize their reactivity with their desired substrate, increasing the efficiency of biological reactions. The <scene name='Sandbox_39/Elements/1'>composition of lysozyme</scene> can be seen on the left, with the carbon atoms outlined in gray, oxygen atoms in red, nitrogen atoms in blue, sulfur atoms in yellow, and the three-letter abbreviation for the <scene name='Sandbox_39/Amino_acid_residues/1'>amino acid residues</scene> in purple.

Lysozyme, like all proteins, also contains a <scene name='Sandbox_39/C_and_n_terminal_residues/1'> 3'C and 5'N terminal </scene>, and these can be seen by following the colors of the rainbow across the molecule. Starting at the red end, the 3' C terminal end, one can work the entire way through to the 5' N terminal end, showing the folding pattern and chain of the protein.

== Secondary Structure ==

Lysozyme contains five <scene name='Sandbox_38/A/2'>alpha helical</scene> regions and five regions containing <scene name='Sandbox_38/B/1'>beta sheets</scene> as displayed in this <scene name='Sandbox_38/Alphab/1'>image</scene>. Linking these secondary structures, a number of beta turns and a large number of random coils make up the remainder of the polypeptide backbone. The polypeptide backbone of lysozyme involved in the 3 antiparallel beta sheets display the beta hairpin motif of supersecondary structure. This depiction of lysozyme contains an antiparallel beta-pleated sheet, which contributes greatly to the stability of the molecule by providing the correct alignment of hydrogen bonds. Lysozyme also contains a great deal of random coil, which is seen in the white regions of the molecule.

'''Hydrogen Bonding'''

In all proteins <scene name='Sandbox_39/Hydrogen_bonds/2'>hydrogen bonds</scene> are essential for stability. In this ribbon diagram, the hydrogen bonds can be seen between the secondary structures of lysozyme highlighted in orange. Since the double bonds of the alpha carbons in the main chain of lysozyme cause torsional strain, lysozyme is limited to very specific hydrogen bonding between the amino acid residues. This representation clearly shows how crucial hydrogen bonding is to help maintain the stability of the protein.

==Amino Acid Residues==

The amino acids present in the lysozyme polypeptide sequence have a direct influence not only on primary structure, but also on the secondary and tertiary structures, which can be influenced by polarity and charge of the sidechains. The various amino acid residues
differ in their properties because of the great variety of side chains present on each amino acid. Polar and nonpolar (and charged and uncharged) side chains lead to various degrees of hydrophobicity and hydrophilicity, which affects protein folding. In lysozyme, the <scene name='Hen_Egg-White_(HEW)_Lysozyme/Residue/1'>residues</scene> that interact with substrate are displayed.

= Bonding Interactions =

'''Disulfide Bonding in Lysozyme'''

Lysozyme contains four <scene name='Sandbox_39/Disulfide_bonds/1'>disulfide bonds</scene> involving eight cysteine residues, which are highlighted in yellow on the left. Disulfide bonds are intramolecular forces that stabilize the tertiary structure of many proteins. Disulfide bonds are present in four locations in lysozyme: between Cys 6 and Cys 127, between Cys 30 and Cys 115, between Cys 64 and Cys 80 and between Cys 76 and Cys 94.

<applet load='1hew' size='350' frame='true' align='left' caption='' />

= Intermolecular Interactions =

'''Hydrophobicity'''

Lysozyme contains both hydrophobic and hydrophilic regions ( <scene name='Sandbox_39/Hydrophobicity/2'>Hydrophobicity</scene> ). The hydrophilic effect, or the desire for proteins to be at a specific position regarding water, is the single most important determinant of protein folding. These regions can be displayed with the hydrophobic regions in gray and the polar, hydrophillic regions in purple. This coloration highlights the location of these regions, showing that the majority of the hydrophobic regions are inside of the protein and that the majority of the hydrophillic regions are on the outside of the protein.

'''Polarity'''

The nature of the amino acid sidechains in the lysozyme polypeptide sequence leads to regions of varying hydrophobicities and polarities of the enzyme structure. The presence of certain regions of hydrophilicity and hydrophobicity is a driving force in determining protein structure when folding. The varying polarities of the side chains influence the locations of residues in the enzyme structure. Nonpolar residues appear blue, and polar residues appear red in the following <scene name='Sandbox_38/Non_polar_blue/1'>polarity</scene> display of lysozyme. Nonpolar residues will display hydrophobic tendencies occurring mostly on the interior of the enzyme while polar residues will increase in abundance on the surface of the protein in order to increase contact with the aqueous solvent so as to satisfy their hydrophilic nature. By observing a space-filled structural depiction of <scene name='Sandbox_38/Non_polar_blu/1'>lysozyme polarity</scene> with polar molecules colored red and nonpolar molecules colored blue the influence of polarity on nucleotide arrangement and protein folding is evident, with the blue (nonpolar) regions inside the red (polar) regions. The presence of <scene name='Sandbox_39/Water/1'>water</scene> interacting with the various hydrophilic residues is depicted to further display how polarity affects structure. Water is depicted as yellow, and the polar and nonpolar regions remain their respective color.

'''Charge'''

Charges of the various regions of the lysozyme structure display a hydrophilic nature and thus also affect the location of that region of polypeptides and the overall folding of the protein. Charged regions of the protein will display hydrophilic tendencies and therefore will most often be located on the surface of the lysozyme molecule where they can interact with the aqueous solvent. Non-charged portions will display hydrophobic tendencies and be located on the interior of the molecule. The effect of various <scene name='Sandbox_38/Rb/1'>charges</scene> on protein structure can be visualized with charged molecules represented by red anionic and blue cationic regions, and uncharged regions colored in grey. This depiction of lysozyme uses a spacefill representation of lysozyme to depict <scene name='Sandbox_38/Chargeddd/1'>charges</scene>.

= Applications of Lysozyme =

Since lysozyme has been widely recognized for its antibacterial and antifungal properties, it has a wide variety of uses both in biochemical and pharmaceutical applications. In molecular biology, lysozyme is often used in the alkaline-lysis procedure for extracting and isolating plasmid DNA. It is used extensively in the pharmaceutical field for destroying gram-positive bacteria, and can be used to support already-existing immune defenses to fight bacterial infections. This enzyme is particularly important for preventing bacterial diseases in infants. Because of its antibacterial properties, lysozyme can also be used in the food industry to help prevent spoilage of foods.

= Discovery and Applications of Hen Egg-White Lysozyme=

<applet load='aln_1H6M_to_1HEW_2.pdb' size='300' frame='true' align='right' caption=' Hen Egg White (HEW) Lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to the active site, PDBid 1HEW' scene='User:Judy_Voet/Lysozyme/Lysozyme1/16' />
Lysozyme was the first enzyme whose X-ray structure was determined <ref> PMID 5840126</ref><ref>Phillips, D. C. The hen egg white lysozyme molecule. Proc. Natl Acad. Sci. USA 57, 483-495 (1967)</ref>. This <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>scene </scene> shows Hen Egg White (HEW) lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to a cleft in the enzyme. David Phillips, who determined the structure in 1965, saw that the cleft was large enough to fit three more saccharide units.
He therefore built a model extending the trisaccharide to a
<scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> that fits into the cleft, labeling the sugar subsites A-F<ref> coordinates of the model kindly provided by Louise Johnson</ref>. Alternately click on <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>trisaccharide</scene> and <scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> to turn the modeled portion of the hexasaccharide on and off.

The interesting thing about the model was that the only way that the hexasaccharide would fit into the cleft was if the 4th saccharide (in subsite D) was strained into a <scene name='User:Judy_Voet/Lysozyme/Half-chair/2'>half-chair conformation</scene>. This conformation is what would be necessary for the formation of an oxocarbenium ion (oxionium ion). When the model was studied, <scene name='User:Judy_Voet/Lysozyme/Glu_35/1'>Glu 35</scene> was found to be in an ideal location to act as a general acid catalyst, 3.34 Angstroms from the bridging oxygen between the 4th and 5th saccharide units. <scene name='User:Judy_Voet/Lysozyme/Asp_52/2'>Asp 52</scene> appeared to be too far away (2.69 angstroms) in the static lysozyme structure to have formed a covalent bond with C1 of the half-chair model in the D site, and no covalent intermediate had ever been detected, so Phillips proposed that it acted as an electrostatic stabilizer of the oxonium ion (referred to as The Phillips Mechanism).

<applet load='aln_1H6M_to_1HEW_2.pdb' size='200' frame='true' align='left' caption='NAG-2-deoxy-2-fluoro-glucosyl fluoride (NAG2FGlcF) bound to Glu35Gln HEW Lysozyme PDBid 1H6M' scene='User:Judy_Voet/Lysozyme/1h6m/3'/>

Then, in 2001, Stephen Withers published <scene name='User:Judy_Voet/Lysozyme/1h6m/3'>1H6M</scene>,<ref>PMID 11518970</ref> in which Glu 35 had been mutated to Gln to remove the general acid catalyst. The substrate contained NAG-2-fluoro-glucosyl fluoride (NAG2FGlcF). The fluoro group on C-1 does not require acid catalysis to be a good leaving group, and the remaining saccharide, in the absence of the acid necessary to catalyse the second step of the reaction, was demonstrated to form a <scene name='User:Judy_Voet/Lysozyme/Covalent/1'> covalent intermediate</scene>. In this <scene name='User:Judy_Voet/Lysozyme/Superposition/2'>superposition</scene> of the half chair model with 1HEW (greens) and the covalent intermediate in 1H6M (blues), note the relatively small motions of Asp 52 and C1 of the sugar ring in going from the model to the covalent intermediate. to observe the motion from the <scene name='User:Judy_Voet/Lysozyme/Asp52_halfchair/1'>half-chair</scene> to the <scene name='User:Judy_Voet/Lysozyme/Covalent/2'>covalent intermediate</scene> just toggle between the two green links.

== 3D Structures of Lysozyme ==

===Lys===

[[2x0a]], [[3iju]], [[3ijv]], [[3a8z]], [[2w1y]], [[2w1m]], [[2w1x]], [[2w1l]], [[3e3d]], [[3exd]], [[2zq3]], [[2zq4]], [[3b72]], [[3b6l]], [[2z12]], [[2z18]], [[2z19]], [[2vb1]], [[2hu3]], [[2hub]], [[2htx]], [[2hu1]], [[2yvb]], [[2epe]], [[2g4p]], [[2g4q]], [[2cgi]], [[2b5z]], [[2d4k]], [[2d91]], [[2f2n]], [[2fbb]], [[2c8o]], [[2c8p]], [[2a6u]], [[2aub]], [[2blx]], [[2bly]], [[2a7d]], [[2a7f]], [[1wtm]], [[1wtn]], [[1w6z]], [[1vdp]], [[1vdq]], [[1vds]], [[1vdt]], [[1ved]], [[1v7t]], [[1ps5]], [[2cds]], [[1lj3]], [[1lj4]], [[1lje]], [[1ljf]], [[1ljg]], [[1ljh]], [[1lji]], [[1ljj]], [[1ljk]], [[1jis]], [[1jit]], [[1jiy]], [[1jj0]], [[1jj1]], [[1jj3]], [[1iee]], [[1qio]], [[1f0w]], [[1f10]], [[1dpx]], [[1c10]], [[1qtk]], [[1lz8]], [[1lz9]], [[1bhz]], [[1bgi]], [[1bwh]], [[1bwi]], [[1bwj]], [[1bvx]], [[1hsw]], [[1hsx]], [[1lpi]], [[4lzt]], [[3lzt]], [[1aki]], [[1jpo]], [[1rfp]], [[193l]], [[194l]], [[5lym]], [[1lza]], [[3lyt]], [[4lyt]], [[5lyt]], [[6lyt]], [[2lzt]], [[1lzt]], [[1lzh]], [[2lzh]], [[7lyz]], [[1lyz]], [[2lyz]], [[3lyz]], [[4lyz]], [[5lyz]], [[6lyz]] - HEWL – chicken 
[[1xei]], [[1xej]], [[1xek]], [[1uco]], [[1lma]], [[4lym]] – HEWL low hydration 
[[1lsa]], [[1lsb]], [[1lsc]], [[1lsd]], [[1lse]], [[1lsf]], [[1lys]] – HEWL temperature influence 
[[2lym]], [[3lym]] – HEWL pressure influence 
[[132l]] – HEWL methylated 
[[1rcm]] – HEWL 3 S-S form 
[[2xbr]], [[2xbs]]- HEWL– Raman crystallography 
[[2zwb]], [[1io5]], [[1lzn]] - HEWL– Neutron 
[[1gxv]], [[1gxx]], [[1e8l]] - HEWL- NMR 
[[2hs7]], [[2hso]], [[2hs9]]- HEWL– Powder diffraction 
[[1ir7]], [[1ir8]], [[1ir9]], [[1ioq]], [[1ior]], [[1ios]], [[1iot]], [[1flq]], [[1flu]], [[1flw]], [[1fly]], [[1fn5]], [[1kxw]], [[1kxx]], [[1kxy]], [[1uia]], [[1uib]], [[1uic]], [[1uid]], [[1uie]], [[1uif]], [[1uig]], [[1uih]], [[1lsm]], [[1lsn]], [[1hel]], [[1hem]], [[1hen]], [[1heo]], [[1hep]], [[1heq]], [[1her]] – HEWL (mutant) 
[[1lyo]], [[2lyo]], [[3lyo]], [[4lyo]] – HEWL cross-linked 
[[1xft]] - tuLys – turkey - Powder diffraction 
[[1jse]], [[1tew]], [[135l]], [[2lz2]], [[1lz2]] – tuLys 
[[3lz2]] – tuLys - Laue 
[[3ab6]] – Lys + NAG3 – Hard clam 
[[2x8r]] – Lys GH25 – ''Aspergillus fumigatus'' 
[[3mgw]] – Lys G – Atlantic salmon 
[[3gxk]], [[3gxr]] – Lys G + NAG – Atlantic cod 
[[2fbd]] – HfLys 1 
[[3cb7]] – HfLys 2 
[[2zij]], [[2zik]], [[2zil]], [[2nwd]], [[1iwt]], [[1iwu]], [[1iwv]], [[1iww]], [[1iwx]], [[1iwy]], [[1iwz]], [[1jwr]], [[1jsf]], [[1rex]], [[1lz1]] – hLys – human 
[[1w08]], [[1ix0]], [[1ioc]], [[1ip1]], [[1ip2]], [[1ip3]], [[1ip4]], [[1ip5]], [[1ip6]], [[1ip7]], [[1qsw]], [[1gev]], [[1gez]], [[1gf0]], [[1gf3]], [[1gf4]], [[1gf5]], [[1gf6]], [[1gf7]], [[1i1z]], [[1i20]], [[1i22]], [[1gfr]], [[1gft]], [[1gfu]], [[1gfv]], [[1gf8]], [[1gf9]], [[1gfa]], [[1gfe]], [[1gfg]], [[1gfh]], [[1gfj]], [[1gfk]], [[1inu]], [[1gdx]], [[1ge0]], [[1ge1]], [[1ge2]], [[1ge3]], [[1ge4]], [[1gdw]], [[1gaz]], [[1gb0]], [[1gb2]], [[1gb3]], [[1gb5]], [[1gb6]], [[1gb7]], [[1gb8]], [[1gb9]], [[1gbo]], [[1gbw]], [[1gbx]], [[1gby]], [[1gbz]], [[1gay]], [[1eq4]], [[1eq5]], [[1eqe]], [[1c7p]], [[1di3]], [[1di4]], [[1di5]], [[1c43]], [[1c45]], [[1c46]], [[1ckg]], [[1cj6]], [[1cj7]], [[1cj8]], [[1cj9]], [[1ckc]], [[1ckd]], [[1ckf]], [[1ckh]], [[1b5z]], [[1b70]], [[1b7q]], [[1b7r]], [[1b7s]], [[1b7l]], [[1b7m]], [[1b7n]], [[1b7p]], [[1b5u]], [[1b5v]], [[1b5w]], [[1b5x]], [[1b5y]], [[1bb3]], [[1bb4]], [[2bqa]], [[2bqb]], [[2bqc]], [[2bqd]], [[2bqe]], [[2bqf]], [[2bqg]], [[2bqh]], [[2bqi]], [[2bqj]], [[2bqk]], [[2bql]], [[2bqm]], [[2bqn]], [[2bqo]], [[2mea]], [[2meb]], [[2mec]], [[2med]], [[2mee]], [[2mef]], [[2meg]], [[2meh]], [[2mei]], [[1wqm]], [[1wqn]], [[1wqo]], [[1wqp]], [[1wqq]], [[1wqr]], [[2heb]], [[2hea]], [[2hec]], [[2hed]], [[2hee]], [[2hef]], [[1jka]], [[1jkb]], [[1jkc]], [[1jkd]], [[1loz]], [[1lyy]], [[1oua]], [[1oub]], [[1ouc]], [[1oud]], [[1oue]], [[1ouf]], [[1oug]], [[1ouh]], [[1oui]], [[1ouj]], [[207l]], [[208l ]], [[1yam]], [[1yan]], [[1yao]], [[1yap]], [[1yaq]], [[1lmt]], [[1lhh]], [[1lhi]], [[1lhj]], [[1lhk]], [[1lhl]], [[133l]], [[134l]], [[1lz4]], [[1lz5]], [[1lz6]], [[1laa]], [[1tay]], [[1tby]], [[1tcy]], [[1tdy]], [[2lhm]], [[3lhm]] – hLys (mutant) 
[[1iy3]], [[1iy4]] – hLys - NMR 
[[2z2f]] – Lys – Bovine 
[[2cwi]], [[1el1]], [[1qqy]] – dLys - dog 
[[2z2e]] – dLys (mutant) 
[[1i56]] – dLys – NMR 
[[2dqa]] – Lys – ''Tapes japonica'' 
[[2gv0]] – Lys – Soft-shelled turtle 
[[1ivm]] – mLys M – NMR – mouse 
[[1jfx]] – Lys – ''Streptomyces coelicolor'' 
[[1gd6]] – Lys – ''Bombyx mori'' 
[[1jug]] – Lys – Echidna 
[[1dkj]] – BqLys – Bobwhite quail 
[[2ihl]] – Lys – Japanese quail 
[[1gbs]] – BsLys – Black swan 
[[1lmn]] – RtLys – Rainbow trout 
[[2eql]] – Lys – horse 
[[1ghl]] – phLys – pheasant 
[[1hhl]] – GfLys – Guinea fowl 
[[1lhm]] – Lys (mutant) – yeast 

===Lys small molecules complexes===

[[3fe0]], [[2d4i]], [[2d4j]], [[1v7s]] - HEWL+ D2O 
[[3m3u]] – HEWL Trp fluorescence 
[[2xjw]] - HEWL + CO 
[[1hf4]], [[1lks]] – HEWL + NO3 
[[3a34]], [[3ems]] - HEWL + arginine 
[[2xth]] – cLys + inhibitor K2PtBr6 
[[3a90]], [[3a91]], [[3a92]], [[3a93]], [[3a94]], [[3a95]], [[3a96]], [[3kam]], [[2pc2]], [[2bpu]], [[1t3p]], [[1h87]] – HEWL + rare earth 
[[2d6b]], [[2hg0]], [[1vat]], [[1gwd]], [[1b2k]], [[1lkr]], [[1azf]], [[8lyz]]- HEWL+ halogen 
[[1vat]] - HEWL + Xe 
[[1n4f]] - HEWL + As 
[[2i6z]] - HEWL + Pt drug 
[[2zyp]] - HEWL + poly (allyl amine) 
[[2f30]], [[2f4a]] – HEWL + urea derivative 
[[2f4g]], [[1ykx]], [[1yky]], [[1ykz]], [[1yl0]], [[1yl1]], [[1z55]] - HEWL + alcohol 
[[1dpw]] – HEWL + MPD 
[[1lcn]] – HEWL + SCN 
[[2zxs]] - HEWL with glycine-amide 
[[2h9j]], [[2h9k]], [[1yik]], [[1yil]] - HEWL + cyclam derivative 
[[1b0d]] – HEWL + p-toluene-sulfonate 
[[2q0m]] - HEWL + tricarbonylmanganese 
[[2war]] – HEWL (mutant) + chitopentaose 
[[2h5z]] – HfLys 1 + chitotetraose – House fly 
[[1hnl]] – hLys + glutathione 
[[1dkk]] – BqLys + NO3 

===Lys complex with glucoside===

[[3a3q]] – HEWL (mutant) + NAG 
[[1sf4]], [[1sf6]], [[1sf7]], [[1sfb]], [[1sfg]], [[1ja2]], [[1ja4]], [[1ja6]], [[1ja7]] – HEWL + NAG oligosaccharide – Powder diffraction 
[[1ubz]], [[1d6p]], [[1d6q]], [[1bb5]] – hLys (mutant) + glycoside 
[[1uc0]], [[1re2]], [[1rem]], [[1rey]], [[1rez]], [[1lzr]], [[1lzs]] - hLys + glycoside 
[[1ljn]], [[1jef]], [[1lzy]] – tuLys + glycoside 
[[1h6m]], [[1at5]], [[1at6]], [[1lzb]], [[1lzc]], [[1lzd]], [[1lze]], [[1lzg]], [[1hew ]]– HEWL + glycoside 
[[1lsy]], [[1lsz]] - HEWL (mutant) + glycoside 
[[1bb6]], [[1bb7]] – RtLys + glycoside 
[[1lmc]] – RtLys + bulgecin 
[[1lmo]], [[1lmp]], [[1lmq]] – RtLys + glucoside 
[[1lsp]] – BsLys + bulgecin 
[[153l]], [[154l]] – Lys +glucoside – goose 

===Phage Lys===

[[2oe4]], [[2oe7]], [[2oe9]], [[2oea]], [[1swz]], [[1cx6]], [[1qtc]], [[1qtd]], [[1qth]], [[1qsb]], [[1qs5]], [[1qs9]], [[1qtb]], [[256l]], [[206l]], [[167l]], [[168l]], [[169l]], [[170l]], [[171l]], [[172l]], [[173l]], [[174l]], [[175l]], [[176l]], [[177l]], [[178l]], [[181l]], [[182l]], [[183l]], [[184l]], [[185l]], [[186l]], [[187l]], [[188l]], [[1nhb]], [[137l]], [[216l]], [[152l]], [[149l]], [[150l]], [[151l]], [[1lyd]], [[2lzm]] - T4Lys – Enterobacteria phage T4 
[[138l]] – T4Lys cross-linked 
[[4lzm]], [[5lzm]], [[6lzm]], [[7lzm]] – T4Lys ionic strength 
[[3l2x]], [[3k2r]], [[3g3v]], [[3g3w]], [[3g3x]], [[2q9d]], [[2q9e]], [[2igc]], [[2ntg]], [[2nth]], [[2ou8]], [[2ou9]], [[1zur]], [[1zwn]], [[1zyt]], [[2cuu]], [[2a4t]] – T4Lys (mutant) spin labeled 
[[3l64]], [[3hwl]], [[3jr6]], [[3gui]], [[3c7w]], [[3c7y]], [[3c7z]], [[3c80]], [[3c81]], [[3c82]], [[3c83]], [[3c8q]], [[3c8r]], [[3c8s]], [[3cdo]], [[3cdq]], [[3cdr]], [[3cdt]], [[3cdv]], [[3f8v]], [[3f9l]], [[3fa0]], [[3fad]], [[3fi5]], [[3dke]], [[3dmv]], [[2o4w]], [[2o79]], [[2o7a]], [[2huk]], [[2hul]], [[2hum]], [[2b7x]], [[2b6t]], [[2b6w]], [[2b6x]], [[2b6y]], [[2b6z]], [[2b70]], [[2b72]], [[2b73]], [[2b74]], [[2b75]], [[1sx7]], [[1swy]], [[1sx2]], [[1t6h]], [[1ssw]], [[1ssy]], [[1t8f]], [[1t8g]], [[1t8a]], [[1t97]], [[1p56]], [[1p5c]], [[1p2l]], [[1p2r]], [[1p36]], [[1p37]], [[1p3n]], [[1p46]], [[1p64]], [[1p6y]], [[1p7s]], [[1pqd]], [[1pqi]], [[1pqj]], [[1pqk]], [[1pqm]], [[1pqo]], [[1oyu]], [[1ks3]], [[1kw5]], [[1kw7]], [[1ky0]], [[1ky1]], [[1l0j]], [[1l0k]], [[1lw9]], [[1lwg]], [[1lwk]], [[1lpy]], [[1llh]], [[1lgu]], [[1li6]], [[1jtm]], [[1jtn]], [[1jqu]], [[1kni]], [[1g06]], [[1g07]], [[1g0g]], [[1g0j]], [[1g0k]], [[1g0l]], [[1g0m]], [[1g0p]], [[1g0q]], [[1g1v]], [[1g1w]], [[1i6s]], [[257l]], [[258l]], [[260l]], [[1epy]], [[1b6i]], [[1cu6]], [[1d9w]], [[1ctw]], [[1cu0]], [[1cu2]], [[1cu3]], [[1cu5]], [[1cv1]], [[1cv4]], [[1cv5]], [[1cv6]], [[1cvk]], [[1cx7]], [[1d2w]], [[1d2y]], [[1d3f]], [[1d3j]], [[1d3m]], [[1d3n]], [[1cv3]], [[1qt3]], [[1qt4]], [[1qt5]], [[1qt6]], [[1qt7]], [[1qt8]], [[1qtv]], [[1qtz]], [[1qud]], [[1qug]], [[1quh]], [[1quo]], [[1qsq]], [[261l]], [[262l]], [[259l]], [[220l]], [[222l]], [[223l]], [[225l]], [[226l]], [[227l]], [[228l]], [[229l]], [[235l]], [[236l]], [[237l]], [[238l]], [[239l]], [[240l]], [[241l]], [[242l]], [[243l]], [[244l]], [[245l]], [[246l]], [[247l]], [[248l]], [[249l]], [[250l]], [[251l]], [[252l]], [[253l]], [[254l]], [[255l]], [[230l]], [[231l]], [[232l]], [[233l]], [[234l]], [[209l]], [[210l]], [[211l]], [[212l]], [[213l]], [[214l]], [[215l]], [[218l]], [[219l]], [[180l]], [[195l]], [[196l]], [[197l]], [[198l]], [[199l]], [[200l]], [[190l]], [[191l]], [[192l]], [[189l]], [[155l]], [[156l]], [[157l]], [[158l]], [[159l]], [[160l]], [[161l]], [[162l]], [[163l]], [[164l]], [[165l]], [[166l]], [[129l]], [[130l]], [[131l]], [[140l]], [[141l]], [[142l]], [[143l]], [[144l]], [[145l]], [[146l]], [[147l]], [[201l]], [[205l]], [[221l]], [[224l]], [[102l]], [[103l]], [[104l]], [[107l]], [[108l]], [[109l]], [[110l]], [[111l]], [[112l]], [[113l]], [[114l]], [[115l]], [[118l]], [[119l]], [[120l]], [[122l]], [[123l]], [[125l]], [[126l]], [[127l]], [[128l]], [[1dya]], [[1dyb]], [[1dyc]], [[1dyd]], [[1dye]], [[1dyf]], [[1dyg]], [[1l00]], [[1l85]], [[1l86]], [[1l87]], [[1l88]], [[1l89]], [[1l90]], [[1l91]], [[1l92]], [[1l93]], [[1l94]], [[1l95]], [[1l96]], [[1l97]], [[1l98]], [[1l99]], [[1lye]], [[1lyf]], [[1lyg]], [[1lyh]], [[1lyi]], [[1lyj]], [[217l]], [[1tla]], [[1l77]], [[1l79]], [[1l80]], [[1l81]], [[1l82]], [[2l78]], [[1l36]], [[1l37]], [[1l38]], [[1l39]], [[1l40]], [[1l41]], [[1l42]], [[1l43]], [[1l44]], [[1l45]], [[1l46]], [[1l47]], [[1l48]], [[1l49]], [[1l50]], [[1l51]], [[1l52]], [[1l53]], [[1l54]], [[1l55]], [[1l56]], [[1l57]], [[1l58]], [[1l59]], [[1l60]], [[1l61]], [[1l62]], [[1l63]], [[1l64]], [[1l65]], [[1l66]], [[1l67]], [[1l68]], [[1l69]], [[1l70]], [[1l71]], [[1l72]], [[1l73]], [[1l74]], [[1l75]], [[1l76]], [[1l17]], [[1l18]], [[1l19]], [[1l20]], [[1l21]], [[1l22]], [[1l23]], [[1l24]], [[1l25]], [[1l26]], [[1l27]], [[1l28]], [[1l29]], [[1l30]], [[1l31]], [[1l32]], [[1l33]], [[1l34]], [[1l35]], [[3lzm]], [[1l01]], [[1l02]], [[1l03]], [[1l04]], [[1l05]], [[1l06]], [[1l07]], [[1l08]], [[1l09]], [[1l10]], [[1l11]], [[1l12]], [[1l13]], [[1l14]], [[1l15]], [[1l16]] – T4Lys (mutant) 
[[1c60]], [[1c61]], [[1c62]], [[1c63]], [[1c64]], [[1c65]], [[1c66]], [[1c67]], [[1c68]], [[1c69]], [[1c6a]], [[1c6b]], [[1c6c]], [[1c6d]], [[1c6e]], [[1c6f]], [[1c6g]], [[1c6h]], [[1c6i]], [[1c6j]], [[1c6k]], [[1c6l]], [[1c6m]], [[1c6n]], [[1c6p]], [[1c6q]], [[1c6t]] - T4Lys (mutant) + noble gas 
[[3ht6]], [[3ht7]], [[3ht8]], [[3ht9]], [[3htb]], [[3hu8]], [[3huq]], [[3guj]], [[3guk]], [[3gul]], [[3gum]], [[3gun]], [[3guo]], [[3gup]], [[3dmx]], [[3dmz]], [[3dn0]], [[3dn1]], [[3dn2]], [[3dn3]], [[3dn4]], [[3dn6]], [[3dn8]], [[3dna]], [[2rb1]], [[2ray]], [[2raz]], [[2rb0]], [[2rb2]], [[2rbn]], [[2rbo]], [[2rbq]], [[2rbr]], [[2rbs]], [[2oty]],[[2otz]], [[1owy]], [[1owz]], [[1ov5]], [[1ov7]], [[1ovh]], [[1ovj]], [[1ovk]], [[1lgw]], [[1lgx]], [[1li2]], [[1li3]], [[1l83]], [[1l84]] – T4Lys (mutant) + benzene derivative 
[[3htd]], [[3htf]], [[3htg]], [[3hu9]], [[3hua]], [[3huk]], [[3hh3]], [[3hh4]], [[3hh5]], [[3hh6]], [[2rbp]], [[2ou0]], [[2f2q]], [[2f32]], [[2f47]], [[1xep]] – T4Lys (mutant) + inhibitor 
[[148l]] - T4Lys (mutant) + glucoside 
[[3d3d]], [[1d9u]] – lamLys + chitohexasaccharide 
[[1am7]] – lamLys - Enterobacteria phage λ 
[[2anv]], [[2anx]] – Lys (mutant)]] - Enterobacteria phage p22 
[[1xjt]], [[1xju]] - Lys - Enterobacteria phage p1 
[[1lba]] - T7Lys - Enterobacteria phage T7 

===Lys protein complex===

[[3m18]], [[3g3a]], [[3g3b]] - HEWL + Variable lymphocyte receptor – Marine lamprey 
[[3a67]], [[3a6b]], [[3a6c]], [[2yss]], [[2eiz]], [[2dqc]], [[2dqd]], [[2dqe]], [[2dqf]], [[2dqg]], [[2dqh]], [[2dqi]], [[2dqj]], [[1j1o]], [[1j1p]], [[1j1x]], [[1ic4]], [[1ic5]], [[1ic7]] – HEWL + mLys antibody HYHEL-10 (mutant) 
[[1xgp]], [[1xgq]], [[1xgr]], [[1xgt]], [[1xgu]] – HEWL + mLys antibody HYHEL-63 
[[3d9a]], [[2eks]], [[1ua6]], [[1c08]], [[3hfm]] – HEWL + mLys antibody HYHEL-10 
[[1uac]] - tuLys C + mLys antibody HYHEL-10 
[[1yqv]], [[2iff]] – HEWL + mLys antibody HYHEL-5 
[[1bql]] – BqLys + mLys antibody HYHEL-5 
[[1ndg]] – HEWL + mLys antibody HYHEL-8 
[[1ndm]] – HEWL + mLys antibody HYHEL-26 
[[1dqj]] - HEWL + mLys antibody HYHEL-63 
[[1nby]], [[1nbz]] – HEWL (mutant) + mLys antibody HYHEL-63 
[[1g7h]], [[1g7i]], [[1g7j]], [[1g7l]], [[1g7m]], [[1kip]], [[1kiq]], [[1kir]] – HEWL + mAnti-HEWL monoclonal antibody (mutant) 
[[1mlc]], [[1vfb]] - HEWL + mIGG1-κ D44.1 FAB 
[[1a2y]] - HEWL (mutant) + mIGG1-κ D1.3 FV 
[[1fdl]] - HEWL + mIGG1-κ D1.3 FAB 
[[1jhl]] – phLys + mIGG1-κ D11.15 FV 
[[1fbi]] – GfLys + mIGG1 F9.13.7 FAB 
[[2znw]], [[2znx]] – HEWL + hSCFV10 antibody 
[[1bvk]] - HEWL + hAnti Lys FV antibody 
[[1dzb]] – tuLys + mSCFV 1F9 
[[1zv5]], [[1zvh]], [[1zvy]], [[1zmy]], [[1ri8]], [[1rjc]], [[1xfp]], [[1jtp]], [[1jtt]], [[1jto]], [[1mel]] - HEWL + cAntibody heavy chain domain – camel 
[[1op9]] - hLys C + cAntibody heavy chain domain 
[[3otp]] – HEWL + EcProtease DO – ''Escherichia coli'' 
[[3f6z]] - HEWL + MLIC – ''Pseudomonas aeruginosa'' 
[[3eba]] – hLys C + hCABHUL6 
[[2qb0]], [[2qar]] – T4Lys/E80 TELSAM domain 
[[2i25]], [[2i26]] - HEWL +NsAntigen receptor PBLA8 variable domain – Nurse shark 
[[1sq2]], [[1t6v]] – HEWL +NsNew Antigen receptor variable domain 
[[1gpq]] – HEWL + EcInhibitor of Vertebrate Lys 
[[1aro]] – T7Lys + T7 RNA polymerase 

===Some Useful External Links===
[http://en.wikipedia.org/wiki/Lysozyme Lysozyme]

[http://en.wikipedia.org/wiki/Glycoside_hydrolase#Retaining_glycoside_hydrolases Retaining Glycoside Hydrolases]

===References===
<references/>

Hen Egg-White (HEW) Lysozyme

2011-04-20T18:31:03Z

Anne Goodling:

'''Introduction'''

Lysozyme - also known as muramidase, or glycoside hydrolase - is a powerful enzyme of biological significance found in abundance in tears, saliva, and human milk. In humans, it is encoded in the ''LYZ'' gene. Although it is responsible for the initial digestion of starches in the mouth, it is most widely identified as a non-specific defense in gram positive bacteria and in many species of fungi. Due to its antibacterial effects, it is a strong component of the innate immune system, and is an important part of an infant's diet to ward off diarrheal diseases. Since it is a small, easily available, and highly stable protein containing only 129 amino acid residues, it has been subject to extensive research regarding its function and structure. Hen Egg White (HEW) Lysozyme is shown below.

===History===

Lysozyme is an enzyme known for its unique ability to degrade the polysaccharide architecture of many kinds of cell walls, normally for the purpose of protection against bacterial infection<ref>Lysozyme. 2010. Citizendium.org. http://en.citizendium.org/wiki/Lysozyme</ref>. Its effects were first noticed by Laschtschenko in 1909. It was officially characterized and termed “lysozyme” by Alexander Fleming, the same person credited for the accidental discovery of penicillin.
The characterization of lysozyme in 1922 by Alexander Fleming was providential in that the undertaken experiment related to the discovery of lysozyme was not geared toward any knowledge of such a protein as lysozyme <ref>Lysozyme. 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>. During the unrelated experiment, nasal drippings were inadvertently introduced to a petri dish containing a bacterial culture, which culture consequently exhibited the results of an as yet unknown enzymatic reaction. The observation of this unknown reaction led to further research on the components of this reaction as well as to the corresponding identification of the newfound "lysozyme." Fleming's discovery was complemented by David C. Phillips' 1965 description of the three-dimensional structure of lysozyme via a 200 pm resolution model obtained from X-ray crystallography <ref>Lysozyme, 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>. Phillips' work was especially groundbreaking since Phillips had managed to successfully elucidate the structure of an enzyme via X-ray crystallography - a feat that had never before been accomplished<ref>Bugg, T. 1997. An Introduction to Enzyme and Coenzyme Chemistry. Blackwell Science Ltd., Oxford </ref>. Phillips' research also led to the first sufficiently described enzymatic mechanism of catalytic action <ref>1967. Proc R Soc Lond B Bio 167 (1009): 389–401.</ref>. Thus, Phillips' elucidation of the function of lysozyme led Phillips to reach a more general conclusion on the diversity of enzymatic chemical action in relation to enzymatic structure. Clearly, the findings of Phillips as well as the more general historical development of the understanding of the structure and function of lysozyme have been paramount to the more general realm of enzyme chemistry.

[[Image:nag-nam2.jpg|thumb|left|350px|Lysozyme Cleavage Site]]
<ref>Image from: http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/proteins/lysozyme.htm</ref>

'''Function'''

Lysozyme is known for damaging bacterial cell walls by catalyzing the hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid (NAM) and N-acetyl-D-glucosamine (NAG) residues in peptidoglycan, and between N-acetyl-D-glucosamine residues in chitodextrins. In this way, lysozyme is efficient in lysing the cell walls of both bacteria and fungi. The location of cleavage for lysozyme on this architectural theme is the β(1-4) glycosidic linkage connecting the C1 carbon of NAM to the C4 carbon of NAG.

The particular substrate of preference for this cleavage type is a (NAG-NAM)₃ hexasaccharide, within which substrate occurs the
cleaving target glycosidic bond, NAM₄-β-O-NAG₅. The individual hexasaccharide binding units are designated A-F, with NAM₄-β-O-NAG₅ glycosidic bond cleavage preference corresponding to a D-E unit glycosidic bond cleavage preference.

= Enzymatic Activity of Lysozyme =

Enzymes are designed to attract and to bind specific substrates. The active site of and lysozyme and its specific ligands are described in the following sections

==Mechanistic Features==

'''Zymogen of Lysozyme: Enzymatic Precursor'''

Zymogens are inactive enzyme precursors. Enzymes are developed in an inactive way to prevent the enzyme from digesting the cell that produced it. This process also prevents the enzyme from becoming active in the wrong portion of the body. Lysozyme's zymogen, simply titled “pre-lysozyme,” was sequenced in 1977 by R D Palmiter, J Gagnon, L H Ericsson and K A Walsh, and has since been sequenced much more extensively.

[[Image:jrip.jpg|thumb|left|350px|Mechanism of Lysozyme]]
<ref>Image from: http://www.google.com/imgres?imgurl=http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/pics-and-strucs/lysozyme-mech.gif&imgrefurl=http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/proteins/lysozyme.htm&usg=__ormapG4XKg-tR5GrMSOdSMTV4vE=&h=603&w=801&sz=7&hl=en&start=17&zoom=1&tbnid=nvr9gvFrUILDkM:&tbnh=143&tbnw=189&prev=/images%3Fq%3DThe%2Blysozyme%2Breaction%2Bmechanism%26um%3D1%26hl%3Den%26sa%3DN%26biw%3D1280%26bih%3D647%26tbs%3Disch:10%2C304&um=1&itbs=1&iact=hc&vpx=521&vpy=349&dur=448&hovh=191&hovw=254&tx=140&ty=48&ei=JQ_LTPKzLIjCsAPkzt2KDg&oei=IA_LTP74OsG78gapm-GFAQ&esq=2&page=2&ndsp=18&ved=1t:429,r:2,s:17&biw=1280&bih=647</ref>

'''Mechanism'''

The lysozyme mechanism of action results in the hydrolysis of a glycoside (hence the familial distinction of lysozyme as a glycosylase<ref>Lysozyme, 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>), which corresponds to the conversion of an acetal to a hemiacetal, which reaction (general degradation of glycosidic bond to units "capped" by newly formed hydroxyl groups) necessitates acid catalysis, since the conversion of acetal to hemiacetal involves the protonation of the reactant oxygen prior to actual bond cleavage. <ref>Pratt, C.W., Voet, D., Voet, J.G. Fundamentals of Biochemistry - Life at the Molecular Level - Third Edition. Voet, Voet and Pratt, 2008.</ref>. Furthermore, the transition state obtained from this protonation is a covalent, oxonium ion, intermediate that must obtain resonance stabilization. The need for some means of acid catalysis and covalent resonance stabilization is adequately provided by the Glu 35 and Asp 52 residues of lysozyme, respectively. The reaction mechanism of lysozyme is demonstrated below. In the following image, the reaction begins at the upper left-hand side, and proceeds according to reaction arrows.

As seen to the left, lysozyme works by hydrolyzing the glycosidic bond, distorting the bond between the NAM and NAG. This produces a glycosyl enzyme intermediate, which reacts with a water molecule to produce the product and the unchanged enzyme.

'''Active Site'''

The <scene name='Hen_Egg-White_(HEW)_Lysozyme/Act_site/2'>active site</scene> of lysozyme is formulated as a prominent cleft outlined by the two aforementioned catalytic amino acids, Glu 35 and Asp 52. The active site is geometrically bent to augment ligand binding, and the two amino acids interact with the ligand in the binding site. Asp52 is depicted in red, and Glu35 is depicted in green.

<applet load='1hew' size='350' frame='true' align='right' caption='' />

==Binding==
'''Ligands'''

A ligand is able to bind to the active site of an enzyme to form a biologically relevant complex. The model to the right shows a space-filling model of lysozyme with the protein distinguishable in brown and the ligand distinguishable in green. Another model of the ligand can be seen in this
<scene name='Hen_Egg-White_(HEW)_Lysozyme/Ligand/1'>ribbon diagram</scene>, with the ligand protruding as a space-filling model from the active site. Here, it is clear that the ligand is a polysaccharide.

The lysozyme reaction is characterized by hydrolysis of the beta (1-4) glycosidic bond between NAM and NAG. Lysozyme has a very specific active site, which can bind only six sugar rings from a polysaccharide chain. Once lysozyme binds to this chain, it hydrolyzes them. These six sugar rings represent the ligand of lysozyme. The lysozyme then distorts the fourth sugar in the six-membered complex, producing stress on the molecule and breaking the glycosidic bond.

The amino acid side-chains Glu35 and Asp52 are critical to the activity of this enzyme. Glu35 acts as a proton donor to the glycosidic bond, cleaving the C-O bond in the substrate, and Asp52 acts as a nucleophile to generate a glycosyl enzyme intermediate. The glycosyl enzyme intermediate then reacts with a water molecule to give the product of hydrolysis.

'''Inhibitors'''

Lysozyme is best inhibited by small saccharides which act competitively with the natural substrate. The smaller saccharides will bind to the first three binding sites of the cleft (sites A-C), but will not reach sites D and E, where the enzyme cuts the glycosidic bond. So, the competitive inhibitor will stick in the cleft, not allowing the substrate to bind to the enzyme complex.<ref>http://mcdb-webarchive.mcdb.ucsb.edu/sears/biochemistry/tw-enz/lysozyme/HEWL/lysozyme-overview.htm</ref> Several known inhibitors of lysozyme are: SDS, N-acetyl-D-glucosamine, and various alcohols and oxidizing agents.<ref>http://www.worthington-biochem.com/ly/default.html</ref>

<applet load='1hew' size='350' frame='true' align='left' caption='' />

= Composition and Structure of Lysozyme =

All proteins consist of carbon, hydrogen, nitrogen, oxygen, and sulfur, as do most organic molecules. Enzymes are composed in such a way as to maximize their reactivity with their desired substrate, increasing the efficiency of biological reactions. The <scene name='Sandbox_39/Elements/1'>composition of lysozyme</scene> can be seen on the left, with the carbon atoms outlined in gray, oxygen atoms in red, nitrogen atoms in blue, sulfur atoms in yellow, and the three-letter abbreviation for the <scene name='Sandbox_39/Amino_acid_residues/1'>amino acid residues</scene> in purple.

Lysozyme, like all proteins, also contains a <scene name='Sandbox_39/C_and_n_terminal_residues/1'> 3'C and 5'N terminal </scene>, and these can be seen by following the colors of the rainbow across the molecule. Starting at the red end, the 3' C terminal end, one can work the entire way through to the 5' N terminal end, showing the folding pattern and chain of the protein.

== Secondary Structure ==

Lysozyme contains five <scene name='Sandbox_38/A/2'>alpha helical</scene> regions and five regions containing <scene name='Sandbox_38/B/1'>beta sheets</scene> as displayed in this <scene name='Sandbox_38/Alphab/1'>image</scene>. Linking these secondary structures, a number of beta turns and a large number of random coils make up the remainder of the polypeptide backbone. The polypeptide backbone of lysozyme involved in the 3 antiparallel beta sheets display the beta hairpin motif of supersecondary structure. This depiction of lysozyme contains an antiparallel beta-pleated sheet, which contributes greatly to the stability of the molecule by providing the correct alignment of hydrogen bonds. Lysozyme also contains a great deal of random coil, which is seen in the white regions of the molecule.

==Amino Acid Residues==

The amino acids present in the lysozyme polypeptide sequence have a direct influence not only on primary structure, but also on the secondary and tertiary structures, which can be influenced by polarity and charge of the sidechains. The various amino acid residues
differ in their properties because of the great variety of side chains present on each amino acid. Polar and nonpolar (and charged and uncharged) side chains lead to various degrees of hydrophobicity and hydrophilicity, which affects protein folding. In lysozyme, the <scene name='Hen_Egg-White_(HEW)_Lysozyme/Residue/1'>residues</scene> that interact with substrate are displayed.

= Bonding Interactions =

'''Disulfide Bonding in Lysozyme'''

Lysozyme contains four <scene name='Sandbox_39/Disulfide_bonds/1'>disulfide bonds</scene> involving eight cysteine residues, which are highlighted in yellow on the left. Disulfide bonds are intramolecular forces that stabilize the tertiary structure of many proteins. Disulfide bonds are present in four locations in lysozyme: between Cys 6 and Cys 127, between Cys 30 and Cys 115, between Cys 64 and Cys 80 and between Cys 76 and Cys 94.

'''Hydrogen Bonding'''

In all proteins <scene name='Sandbox_39/Hydrogen_bonds/2'>hydrogen bonds</scene> are essential for stability. In this ribbon diagram, the hydrogen bonds can be seen between the secondary structures of lysozyme highlighted in orange. Since the double bonds of the alpha carbons in the main chain of lysozyme cause torsional strain, lysozyme is limited to very specific hydrogen bonding between the amino acid residues. This representation clearly shows how crucial hydrogen bonding is to help maintain the stability of the protein.

<applet load='1hew' size='350' frame='true' align='left' caption='' />

= Intermolecular Interactions =

'''Hydrophobicity'''

Lysozyme contains both hydrophobic and hydrophilic regions ( <scene name='Sandbox_39/Hydrophobicity/2'>Hydrophobicity</scene> ). The hydrophilic effect, or the desire for proteins to be at a specific position regarding water, is the single most important determinant of protein folding. These regions can be displayed with the hydrophobic regions in gray and the polar, hydrophillic regions in purple. This coloration highlights the location of these regions, showing that the majority of the hydrophobic regions are inside of the protein and that the majority of the hydrophillic regions are on the outside of the protein.

'''Polarity'''

The nature of the amino acid sidechains in the lysozyme polypeptide sequence leads to regions of varying hydrophobicities and polarities of the enzyme structure. The presence of certain regions of hydrophilicity and hydrophobicity is a driving force in determining protein structure when folding. The varying polarities of the side chains influence the locations of residues in the enzyme structure. Nonpolar residues appear blue, and polar residues appear red in the following <scene name='Sandbox_38/Non_polar_blue/1'>polarity</scene> display of lysozyme. Nonpolar residues will display hydrophobic tendencies occurring mostly on the interior of the enzyme while polar residues will increase in abundance on the surface of the protein in order to increase contact with the aqueous solvent so as to satisfy their hydrophilic nature. By observing a space-filled structural depiction of <scene name='Sandbox_38/Non_polar_blu/1'>lysozyme polarity</scene> with polar molecules colored red and nonpolar molecules colored blue the influence of polarity on nucleotide arrangement and protein folding is evident, with the blue (nonpolar) regions inside the red (polar) regions. The presence of <scene name='Sandbox_39/Water/1'>water</scene> interacting with the various hydrophilic residues is depicted to further display how polarity affects structure. Water is depicted as yellow, and the polar and nonpolar regions remain their respective color.

'''Charge'''

Charges of the various regions of the lysozyme structure display a hydrophilic nature and thus also affect the location of that region of polypeptides and the overall folding of the protein. Charged regions of the protein will display hydrophilic tendencies and therefore will most often be located on the surface of the lysozyme molecule where they can interact with the aqueous solvent. Non-charged portions will display hydrophobic tendencies and be located on the interior of the molecule. The effect of various <scene name='Sandbox_38/Rb/1'>charges</scene> on protein structure can be visualized with charged molecules represented by red anionic and blue cationic regions, and uncharged regions colored in grey. This depiction of lysozyme uses a spacefill representation of lysozyme to depict <scene name='Sandbox_38/Chargeddd/1'>charges</scene>.

= Applications of Lysozyme =

Since lysozyme has been widely recognized for its antibacterial and antifungal properties, it has a wide variety of uses both in biochemical and pharmaceutical applications. In molecular biology, lysozyme is often used in the alkaline-lysis procedure for extracting and isolating plasmid DNA. It is used extensively in the pharmaceutical field for destroying gram-positive bacteria, and can be used to support already-existing immune defenses to fight bacterial infections. This enzyme is particularly important for preventing bacterial diseases in infants. Because of its antibacterial properties, lysozyme can also be used in the food industry to help prevent spoilage of foods.

= Discovery and Applications of Hen Egg-White Lysozyme=

<applet load='aln_1H6M_to_1HEW_2.pdb' size='300' frame='true' align='right' caption=' Hen Egg White (HEW) Lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to the active site, PDBid 1HEW' scene='User:Judy_Voet/Lysozyme/Lysozyme1/16' />
Lysozyme was the first enzyme whose X-ray structure was determined <ref> PMID 5840126</ref><ref>Phillips, D. C. The hen egg white lysozyme molecule. Proc. Natl Acad. Sci. USA 57, 483-495 (1967)</ref>. This <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>scene </scene> shows Hen Egg White (HEW) lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to a cleft in the enzyme. David Phillips, who determined the structure in 1965, saw that the cleft was large enough to fit three more saccharide units.
He therefore built a model extending the trisaccharide to a
<scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> that fits into the cleft, labeling the sugar subsites A-F<ref> coordinates of the model kindly provided by Louise Johnson</ref>. Alternately click on <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>trisaccharide</scene> and <scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> to turn the modeled portion of the hexasaccharide on and off.

The interesting thing about the model was that the only way that the hexasaccharide would fit into the cleft was if the 4th saccharide (in subsite D) was strained into a <scene name='User:Judy_Voet/Lysozyme/Half-chair/2'>half-chair conformation</scene>. This conformation is what would be necessary for the formation of an oxocarbenium ion (oxionium ion). When the model was studied, <scene name='User:Judy_Voet/Lysozyme/Glu_35/1'>Glu 35</scene> was found to be in an ideal location to act as a general acid catalyst, 3.34 Angstroms from the bridging oxygen between the 4th and 5th saccharide units. <scene name='User:Judy_Voet/Lysozyme/Asp_52/2'>Asp 52</scene> appeared to be too far away (2.69 angstroms) in the static lysozyme structure to have formed a covalent bond with C1 of the half-chair model in the D site, and no covalent intermediate had ever been detected, so Phillips proposed that it acted as an electrostatic stabilizer of the oxonium ion (referred to as The Phillips Mechanism).

<applet load='aln_1H6M_to_1HEW_2.pdb' size='200' frame='true' align='left' caption='NAG-2-deoxy-2-fluoro-glucosyl fluoride (NAG2FGlcF) bound to Glu35Gln HEW Lysozyme PDBid 1H6M' scene='User:Judy_Voet/Lysozyme/1h6m/3'/>

Then, in 2001, Stephen Withers published <scene name='User:Judy_Voet/Lysozyme/1h6m/3'>1H6M</scene>,<ref>PMID 11518970</ref> in which Glu 35 had been mutated to Gln to remove the general acid catalyst. The substrate contained NAG-2-fluoro-glucosyl fluoride (NAG2FGlcF). The fluoro group on C-1 does not require acid catalysis to be a good leaving group, and the remaining saccharide, in the absence of the acid necessary to catalyse the second step of the reaction, was demonstrated to form a <scene name='User:Judy_Voet/Lysozyme/Covalent/1'> covalent intermediate</scene>. In this <scene name='User:Judy_Voet/Lysozyme/Superposition/2'>superposition</scene> of the half chair model with 1HEW (greens) and the covalent intermediate in 1H6M (blues), note the relatively small motions of Asp 52 and C1 of the sugar ring in going from the model to the covalent intermediate. to observe the motion from the <scene name='User:Judy_Voet/Lysozyme/Asp52_halfchair/1'>half-chair</scene> to the <scene name='User:Judy_Voet/Lysozyme/Covalent/2'>covalent intermediate</scene> just toggle between the two green links.

== 3D Structures of Lysozyme ==

===Lys===

[[2x0a]], [[3iju]], [[3ijv]], [[3a8z]], [[2w1y]], [[2w1m]], [[2w1x]], [[2w1l]], [[3e3d]], [[3exd]], [[2zq3]], [[2zq4]], [[3b72]], [[3b6l]], [[2z12]], [[2z18]], [[2z19]], [[2vb1]], [[2hu3]], [[2hub]], [[2htx]], [[2hu1]], [[2yvb]], [[2epe]], [[2g4p]], [[2g4q]], [[2cgi]], [[2b5z]], [[2d4k]], [[2d91]], [[2f2n]], [[2fbb]], [[2c8o]], [[2c8p]], [[2a6u]], [[2aub]], [[2blx]], [[2bly]], [[2a7d]], [[2a7f]], [[1wtm]], [[1wtn]], [[1w6z]], [[1vdp]], [[1vdq]], [[1vds]], [[1vdt]], [[1ved]], [[1v7t]], [[1ps5]], [[2cds]], [[1lj3]], [[1lj4]], [[1lje]], [[1ljf]], [[1ljg]], [[1ljh]], [[1lji]], [[1ljj]], [[1ljk]], [[1jis]], [[1jit]], [[1jiy]], [[1jj0]], [[1jj1]], [[1jj3]], [[1iee]], [[1qio]], [[1f0w]], [[1f10]], [[1dpx]], [[1c10]], [[1qtk]], [[1lz8]], [[1lz9]], [[1bhz]], [[1bgi]], [[1bwh]], [[1bwi]], [[1bwj]], [[1bvx]], [[1hsw]], [[1hsx]], [[1lpi]], [[4lzt]], [[3lzt]], [[1aki]], [[1jpo]], [[1rfp]], [[193l]], [[194l]], [[5lym]], [[1lza]], [[3lyt]], [[4lyt]], [[5lyt]], [[6lyt]], [[2lzt]], [[1lzt]], [[1lzh]], [[2lzh]], [[7lyz]], [[1lyz]], [[2lyz]], [[3lyz]], [[4lyz]], [[5lyz]], [[6lyz]] - HEWL – chicken 
[[1xei]], [[1xej]], [[1xek]], [[1uco]], [[1lma]], [[4lym]] – HEWL low hydration 
[[1lsa]], [[1lsb]], [[1lsc]], [[1lsd]], [[1lse]], [[1lsf]], [[1lys]] – HEWL temperature influence 
[[2lym]], [[3lym]] – HEWL pressure influence 
[[132l]] – HEWL methylated 
[[1rcm]] – HEWL 3 S-S form 
[[2xbr]], [[2xbs]]- HEWL– Raman crystallography 
[[2zwb]], [[1io5]], [[1lzn]] - HEWL– Neutron 
[[1gxv]], [[1gxx]], [[1e8l]] - HEWL- NMR 
[[2hs7]], [[2hso]], [[2hs9]]- HEWL– Powder diffraction 
[[1ir7]], [[1ir8]], [[1ir9]], [[1ioq]], [[1ior]], [[1ios]], [[1iot]], [[1flq]], [[1flu]], [[1flw]], [[1fly]], [[1fn5]], [[1kxw]], [[1kxx]], [[1kxy]], [[1uia]], [[1uib]], [[1uic]], [[1uid]], [[1uie]], [[1uif]], [[1uig]], [[1uih]], [[1lsm]], [[1lsn]], [[1hel]], [[1hem]], [[1hen]], [[1heo]], [[1hep]], [[1heq]], [[1her]] – HEWL (mutant) 
[[1lyo]], [[2lyo]], [[3lyo]], [[4lyo]] – HEWL cross-linked 
[[1xft]] - tuLys – turkey - Powder diffraction 
[[1jse]], [[1tew]], [[135l]], [[2lz2]], [[1lz2]] – tuLys 
[[3lz2]] – tuLys - Laue 
[[3ab6]] – Lys + NAG3 – Hard clam 
[[2x8r]] – Lys GH25 – ''Aspergillus fumigatus'' 
[[3mgw]] – Lys G – Atlantic salmon 
[[3gxk]], [[3gxr]] – Lys G + NAG – Atlantic cod 
[[2fbd]] – HfLys 1 
[[3cb7]] – HfLys 2 
[[2zij]], [[2zik]], [[2zil]], [[2nwd]], [[1iwt]], [[1iwu]], [[1iwv]], [[1iww]], [[1iwx]], [[1iwy]], [[1iwz]], [[1jwr]], [[1jsf]], [[1rex]], [[1lz1]] – hLys – human 
[[1w08]], [[1ix0]], [[1ioc]], [[1ip1]], [[1ip2]], [[1ip3]], [[1ip4]], [[1ip5]], [[1ip6]], [[1ip7]], [[1qsw]], [[1gev]], [[1gez]], [[1gf0]], [[1gf3]], [[1gf4]], [[1gf5]], [[1gf6]], [[1gf7]], [[1i1z]], [[1i20]], [[1i22]], [[1gfr]], [[1gft]], [[1gfu]], [[1gfv]], [[1gf8]], [[1gf9]], [[1gfa]], [[1gfe]], [[1gfg]], [[1gfh]], [[1gfj]], [[1gfk]], [[1inu]], [[1gdx]], [[1ge0]], [[1ge1]], [[1ge2]], [[1ge3]], [[1ge4]], [[1gdw]], [[1gaz]], [[1gb0]], [[1gb2]], [[1gb3]], [[1gb5]], [[1gb6]], [[1gb7]], [[1gb8]], [[1gb9]], [[1gbo]], [[1gbw]], [[1gbx]], [[1gby]], [[1gbz]], [[1gay]], [[1eq4]], [[1eq5]], [[1eqe]], [[1c7p]], [[1di3]], [[1di4]], [[1di5]], [[1c43]], [[1c45]], [[1c46]], [[1ckg]], [[1cj6]], [[1cj7]], [[1cj8]], [[1cj9]], [[1ckc]], [[1ckd]], [[1ckf]], [[1ckh]], [[1b5z]], [[1b70]], [[1b7q]], [[1b7r]], [[1b7s]], [[1b7l]], [[1b7m]], [[1b7n]], [[1b7p]], [[1b5u]], [[1b5v]], [[1b5w]], [[1b5x]], [[1b5y]], [[1bb3]], [[1bb4]], [[2bqa]], [[2bqb]], [[2bqc]], [[2bqd]], [[2bqe]], [[2bqf]], [[2bqg]], [[2bqh]], [[2bqi]], [[2bqj]], [[2bqk]], [[2bql]], [[2bqm]], [[2bqn]], [[2bqo]], [[2mea]], [[2meb]], [[2mec]], [[2med]], [[2mee]], [[2mef]], [[2meg]], [[2meh]], [[2mei]], [[1wqm]], [[1wqn]], [[1wqo]], [[1wqp]], [[1wqq]], [[1wqr]], [[2heb]], [[2hea]], [[2hec]], [[2hed]], [[2hee]], [[2hef]], [[1jka]], [[1jkb]], [[1jkc]], [[1jkd]], [[1loz]], [[1lyy]], [[1oua]], [[1oub]], [[1ouc]], [[1oud]], [[1oue]], [[1ouf]], [[1oug]], [[1ouh]], [[1oui]], [[1ouj]], [[207l]], [[208l ]], [[1yam]], [[1yan]], [[1yao]], [[1yap]], [[1yaq]], [[1lmt]], [[1lhh]], [[1lhi]], [[1lhj]], [[1lhk]], [[1lhl]], [[133l]], [[134l]], [[1lz4]], [[1lz5]], [[1lz6]], [[1laa]], [[1tay]], [[1tby]], [[1tcy]], [[1tdy]], [[2lhm]], [[3lhm]] – hLys (mutant) 
[[1iy3]], [[1iy4]] – hLys - NMR 
[[2z2f]] – Lys – Bovine 
[[2cwi]], [[1el1]], [[1qqy]] – dLys - dog 
[[2z2e]] – dLys (mutant) 
[[1i56]] – dLys – NMR 
[[2dqa]] – Lys – ''Tapes japonica'' 
[[2gv0]] – Lys – Soft-shelled turtle 
[[1ivm]] – mLys M – NMR – mouse 
[[1jfx]] – Lys – ''Streptomyces coelicolor'' 
[[1gd6]] – Lys – ''Bombyx mori'' 
[[1jug]] – Lys – Echidna 
[[1dkj]] – BqLys – Bobwhite quail 
[[2ihl]] – Lys – Japanese quail 
[[1gbs]] – BsLys – Black swan 
[[1lmn]] – RtLys – Rainbow trout 
[[2eql]] – Lys – horse 
[[1ghl]] – phLys – pheasant 
[[1hhl]] – GfLys – Guinea fowl 
[[1lhm]] – Lys (mutant) – yeast 

===Lys small molecules complexes===

[[3fe0]], [[2d4i]], [[2d4j]], [[1v7s]] - HEWL+ D2O 
[[3m3u]] – HEWL Trp fluorescence 
[[2xjw]] - HEWL + CO 
[[1hf4]], [[1lks]] – HEWL + NO3 
[[3a34]], [[3ems]] - HEWL + arginine 
[[2xth]] – cLys + inhibitor K2PtBr6 
[[3a90]], [[3a91]], [[3a92]], [[3a93]], [[3a94]], [[3a95]], [[3a96]], [[3kam]], [[2pc2]], [[2bpu]], [[1t3p]], [[1h87]] – HEWL + rare earth 
[[2d6b]], [[2hg0]], [[1vat]], [[1gwd]], [[1b2k]], [[1lkr]], [[1azf]], [[8lyz]]- HEWL+ halogen 
[[1vat]] - HEWL + Xe 
[[1n4f]] - HEWL + As 
[[2i6z]] - HEWL + Pt drug 
[[2zyp]] - HEWL + poly (allyl amine) 
[[2f30]], [[2f4a]] – HEWL + urea derivative 
[[2f4g]], [[1ykx]], [[1yky]], [[1ykz]], [[1yl0]], [[1yl1]], [[1z55]] - HEWL + alcohol 
[[1dpw]] – HEWL + MPD 
[[1lcn]] – HEWL + SCN 
[[2zxs]] - HEWL with glycine-amide 
[[2h9j]], [[2h9k]], [[1yik]], [[1yil]] - HEWL + cyclam derivative 
[[1b0d]] – HEWL + p-toluene-sulfonate 
[[2q0m]] - HEWL + tricarbonylmanganese 
[[2war]] – HEWL (mutant) + chitopentaose 
[[2h5z]] – HfLys 1 + chitotetraose – House fly 
[[1hnl]] – hLys + glutathione 
[[1dkk]] – BqLys + NO3 

===Lys complex with glucoside===

[[3a3q]] – HEWL (mutant) + NAG 
[[1sf4]], [[1sf6]], [[1sf7]], [[1sfb]], [[1sfg]], [[1ja2]], [[1ja4]], [[1ja6]], [[1ja7]] – HEWL + NAG oligosaccharide – Powder diffraction 
[[1ubz]], [[1d6p]], [[1d6q]], [[1bb5]] – hLys (mutant) + glycoside 
[[1uc0]], [[1re2]], [[1rem]], [[1rey]], [[1rez]], [[1lzr]], [[1lzs]] - hLys + glycoside 
[[1ljn]], [[1jef]], [[1lzy]] – tuLys + glycoside 
[[1h6m]], [[1at5]], [[1at6]], [[1lzb]], [[1lzc]], [[1lzd]], [[1lze]], [[1lzg]], [[1hew ]]– HEWL + glycoside 
[[1lsy]], [[1lsz]] - HEWL (mutant) + glycoside 
[[1bb6]], [[1bb7]] – RtLys + glycoside 
[[1lmc]] – RtLys + bulgecin 
[[1lmo]], [[1lmp]], [[1lmq]] – RtLys + glucoside 
[[1lsp]] – BsLys + bulgecin 
[[153l]], [[154l]] – Lys +glucoside – goose 

===Phage Lys===

[[2oe4]], [[2oe7]], [[2oe9]], [[2oea]], [[1swz]], [[1cx6]], [[1qtc]], [[1qtd]], [[1qth]], [[1qsb]], [[1qs5]], [[1qs9]], [[1qtb]], [[256l]], [[206l]], [[167l]], [[168l]], [[169l]], [[170l]], [[171l]], [[172l]], [[173l]], [[174l]], [[175l]], [[176l]], [[177l]], [[178l]], [[181l]], [[182l]], [[183l]], [[184l]], [[185l]], [[186l]], [[187l]], [[188l]], [[1nhb]], [[137l]], [[216l]], [[152l]], [[149l]], [[150l]], [[151l]], [[1lyd]], [[2lzm]] - T4Lys – Enterobacteria phage T4 
[[138l]] – T4Lys cross-linked 
[[4lzm]], [[5lzm]], [[6lzm]], [[7lzm]] – T4Lys ionic strength 
[[3l2x]], [[3k2r]], [[3g3v]], [[3g3w]], [[3g3x]], [[2q9d]], [[2q9e]], [[2igc]], [[2ntg]], [[2nth]], [[2ou8]], [[2ou9]], [[1zur]], [[1zwn]], [[1zyt]], [[2cuu]], [[2a4t]] – T4Lys (mutant) spin labeled 
[[3l64]], [[3hwl]], [[3jr6]], [[3gui]], [[3c7w]], [[3c7y]], [[3c7z]], [[3c80]], [[3c81]], [[3c82]], [[3c83]], [[3c8q]], [[3c8r]], [[3c8s]], [[3cdo]], [[3cdq]], [[3cdr]], [[3cdt]], [[3cdv]], [[3f8v]], [[3f9l]], [[3fa0]], [[3fad]], [[3fi5]], [[3dke]], [[3dmv]], [[2o4w]], [[2o79]], [[2o7a]], [[2huk]], [[2hul]], [[2hum]], [[2b7x]], [[2b6t]], [[2b6w]], [[2b6x]], [[2b6y]], [[2b6z]], [[2b70]], [[2b72]], [[2b73]], [[2b74]], [[2b75]], [[1sx7]], [[1swy]], [[1sx2]], [[1t6h]], [[1ssw]], [[1ssy]], [[1t8f]], [[1t8g]], [[1t8a]], [[1t97]], [[1p56]], [[1p5c]], [[1p2l]], [[1p2r]], [[1p36]], [[1p37]], [[1p3n]], [[1p46]], [[1p64]], [[1p6y]], [[1p7s]], [[1pqd]], [[1pqi]], [[1pqj]], [[1pqk]], [[1pqm]], [[1pqo]], [[1oyu]], [[1ks3]], [[1kw5]], [[1kw7]], [[1ky0]], [[1ky1]], [[1l0j]], [[1l0k]], [[1lw9]], [[1lwg]], [[1lwk]], [[1lpy]], [[1llh]], [[1lgu]], [[1li6]], [[1jtm]], [[1jtn]], [[1jqu]], [[1kni]], [[1g06]], [[1g07]], [[1g0g]], [[1g0j]], [[1g0k]], [[1g0l]], [[1g0m]], [[1g0p]], [[1g0q]], [[1g1v]], [[1g1w]], [[1i6s]], [[257l]], [[258l]], [[260l]], [[1epy]], [[1b6i]], [[1cu6]], [[1d9w]], [[1ctw]], [[1cu0]], [[1cu2]], [[1cu3]], [[1cu5]], [[1cv1]], [[1cv4]], [[1cv5]], [[1cv6]], [[1cvk]], [[1cx7]], [[1d2w]], [[1d2y]], [[1d3f]], [[1d3j]], [[1d3m]], [[1d3n]], [[1cv3]], [[1qt3]], [[1qt4]], [[1qt5]], [[1qt6]], [[1qt7]], [[1qt8]], [[1qtv]], [[1qtz]], [[1qud]], [[1qug]], [[1quh]], [[1quo]], [[1qsq]], [[261l]], [[262l]], [[259l]], [[220l]], [[222l]], [[223l]], [[225l]], [[226l]], [[227l]], [[228l]], [[229l]], [[235l]], [[236l]], [[237l]], [[238l]], [[239l]], [[240l]], [[241l]], [[242l]], [[243l]], [[244l]], [[245l]], [[246l]], [[247l]], [[248l]], [[249l]], [[250l]], [[251l]], [[252l]], [[253l]], [[254l]], [[255l]], [[230l]], [[231l]], [[232l]], [[233l]], [[234l]], [[209l]], [[210l]], [[211l]], [[212l]], [[213l]], [[214l]], [[215l]], [[218l]], [[219l]], [[180l]], [[195l]], [[196l]], [[197l]], [[198l]], [[199l]], [[200l]], [[190l]], [[191l]], [[192l]], [[189l]], [[155l]], [[156l]], [[157l]], [[158l]], [[159l]], [[160l]], [[161l]], [[162l]], [[163l]], [[164l]], [[165l]], [[166l]], [[129l]], [[130l]], [[131l]], [[140l]], [[141l]], [[142l]], [[143l]], [[144l]], [[145l]], [[146l]], [[147l]], [[201l]], [[205l]], [[221l]], [[224l]], [[102l]], [[103l]], [[104l]], [[107l]], [[108l]], [[109l]], [[110l]], [[111l]], [[112l]], [[113l]], [[114l]], [[115l]], [[118l]], [[119l]], [[120l]], [[122l]], [[123l]], [[125l]], [[126l]], [[127l]], [[128l]], [[1dya]], [[1dyb]], [[1dyc]], [[1dyd]], [[1dye]], [[1dyf]], [[1dyg]], [[1l00]], [[1l85]], [[1l86]], [[1l87]], [[1l88]], [[1l89]], [[1l90]], [[1l91]], [[1l92]], [[1l93]], [[1l94]], [[1l95]], [[1l96]], [[1l97]], [[1l98]], [[1l99]], [[1lye]], [[1lyf]], [[1lyg]], [[1lyh]], [[1lyi]], [[1lyj]], [[217l]], [[1tla]], [[1l77]], [[1l79]], [[1l80]], [[1l81]], [[1l82]], [[2l78]], [[1l36]], [[1l37]], [[1l38]], [[1l39]], [[1l40]], [[1l41]], [[1l42]], [[1l43]], [[1l44]], [[1l45]], [[1l46]], [[1l47]], [[1l48]], [[1l49]], [[1l50]], [[1l51]], [[1l52]], [[1l53]], [[1l54]], [[1l55]], [[1l56]], [[1l57]], [[1l58]], [[1l59]], [[1l60]], [[1l61]], [[1l62]], [[1l63]], [[1l64]], [[1l65]], [[1l66]], [[1l67]], [[1l68]], [[1l69]], [[1l70]], [[1l71]], [[1l72]], [[1l73]], [[1l74]], [[1l75]], [[1l76]], [[1l17]], [[1l18]], [[1l19]], [[1l20]], [[1l21]], [[1l22]], [[1l23]], [[1l24]], [[1l25]], [[1l26]], [[1l27]], [[1l28]], [[1l29]], [[1l30]], [[1l31]], [[1l32]], [[1l33]], [[1l34]], [[1l35]], [[3lzm]], [[1l01]], [[1l02]], [[1l03]], [[1l04]], [[1l05]], [[1l06]], [[1l07]], [[1l08]], [[1l09]], [[1l10]], [[1l11]], [[1l12]], [[1l13]], [[1l14]], [[1l15]], [[1l16]] – T4Lys (mutant) 
[[1c60]], [[1c61]], [[1c62]], [[1c63]], [[1c64]], [[1c65]], [[1c66]], [[1c67]], [[1c68]], [[1c69]], [[1c6a]], [[1c6b]], [[1c6c]], [[1c6d]], [[1c6e]], [[1c6f]], [[1c6g]], [[1c6h]], [[1c6i]], [[1c6j]], [[1c6k]], [[1c6l]], [[1c6m]], [[1c6n]], [[1c6p]], [[1c6q]], [[1c6t]] - T4Lys (mutant) + noble gas 
[[3ht6]], [[3ht7]], [[3ht8]], [[3ht9]], [[3htb]], [[3hu8]], [[3huq]], [[3guj]], [[3guk]], [[3gul]], [[3gum]], [[3gun]], [[3guo]], [[3gup]], [[3dmx]], [[3dmz]], [[3dn0]], [[3dn1]], [[3dn2]], [[3dn3]], [[3dn4]], [[3dn6]], [[3dn8]], [[3dna]], [[2rb1]], [[2ray]], [[2raz]], [[2rb0]], [[2rb2]], [[2rbn]], [[2rbo]], [[2rbq]], [[2rbr]], [[2rbs]], [[2oty]],[[2otz]], [[1owy]], [[1owz]], [[1ov5]], [[1ov7]], [[1ovh]], [[1ovj]], [[1ovk]], [[1lgw]], [[1lgx]], [[1li2]], [[1li3]], [[1l83]], [[1l84]] – T4Lys (mutant) + benzene derivative 
[[3htd]], [[3htf]], [[3htg]], [[3hu9]], [[3hua]], [[3huk]], [[3hh3]], [[3hh4]], [[3hh5]], [[3hh6]], [[2rbp]], [[2ou0]], [[2f2q]], [[2f32]], [[2f47]], [[1xep]] – T4Lys (mutant) + inhibitor 
[[148l]] - T4Lys (mutant) + glucoside 
[[3d3d]], [[1d9u]] – lamLys + chitohexasaccharide 
[[1am7]] – lamLys - Enterobacteria phage λ 
[[2anv]], [[2anx]] – Lys (mutant)]] - Enterobacteria phage p22 
[[1xjt]], [[1xju]] - Lys - Enterobacteria phage p1 
[[1lba]] - T7Lys - Enterobacteria phage T7 

===Lys protein complex===

[[3m18]], [[3g3a]], [[3g3b]] - HEWL + Variable lymphocyte receptor – Marine lamprey 
[[3a67]], [[3a6b]], [[3a6c]], [[2yss]], [[2eiz]], [[2dqc]], [[2dqd]], [[2dqe]], [[2dqf]], [[2dqg]], [[2dqh]], [[2dqi]], [[2dqj]], [[1j1o]], [[1j1p]], [[1j1x]], [[1ic4]], [[1ic5]], [[1ic7]] – HEWL + mLys antibody HYHEL-10 (mutant) 
[[1xgp]], [[1xgq]], [[1xgr]], [[1xgt]], [[1xgu]] – HEWL + mLys antibody HYHEL-63 
[[3d9a]], [[2eks]], [[1ua6]], [[1c08]], [[3hfm]] – HEWL + mLys antibody HYHEL-10 
[[1uac]] - tuLys C + mLys antibody HYHEL-10 
[[1yqv]], [[2iff]] – HEWL + mLys antibody HYHEL-5 
[[1bql]] – BqLys + mLys antibody HYHEL-5 
[[1ndg]] – HEWL + mLys antibody HYHEL-8 
[[1ndm]] – HEWL + mLys antibody HYHEL-26 
[[1dqj]] - HEWL + mLys antibody HYHEL-63 
[[1nby]], [[1nbz]] – HEWL (mutant) + mLys antibody HYHEL-63 
[[1g7h]], [[1g7i]], [[1g7j]], [[1g7l]], [[1g7m]], [[1kip]], [[1kiq]], [[1kir]] – HEWL + mAnti-HEWL monoclonal antibody (mutant) 
[[1mlc]], [[1vfb]] - HEWL + mIGG1-κ D44.1 FAB 
[[1a2y]] - HEWL (mutant) + mIGG1-κ D1.3 FV 
[[1fdl]] - HEWL + mIGG1-κ D1.3 FAB 
[[1jhl]] – phLys + mIGG1-κ D11.15 FV 
[[1fbi]] – GfLys + mIGG1 F9.13.7 FAB 
[[2znw]], [[2znx]] – HEWL + hSCFV10 antibody 
[[1bvk]] - HEWL + hAnti Lys FV antibody 
[[1dzb]] – tuLys + mSCFV 1F9 
[[1zv5]], [[1zvh]], [[1zvy]], [[1zmy]], [[1ri8]], [[1rjc]], [[1xfp]], [[1jtp]], [[1jtt]], [[1jto]], [[1mel]] - HEWL + cAntibody heavy chain domain – camel 
[[1op9]] - hLys C + cAntibody heavy chain domain 
[[3otp]] – HEWL + EcProtease DO – ''Escherichia coli'' 
[[3f6z]] - HEWL + MLIC – ''Pseudomonas aeruginosa'' 
[[3eba]] – hLys C + hCABHUL6 
[[2qb0]], [[2qar]] – T4Lys/E80 TELSAM domain 
[[2i25]], [[2i26]] - HEWL +NsAntigen receptor PBLA8 variable domain – Nurse shark 
[[1sq2]], [[1t6v]] – HEWL +NsNew Antigen receptor variable domain 
[[1gpq]] – HEWL + EcInhibitor of Vertebrate Lys 
[[1aro]] – T7Lys + T7 RNA polymerase 

===Some Useful External Links===
[http://en.wikipedia.org/wiki/Lysozyme Lysozyme]

[http://en.wikipedia.org/wiki/Glycoside_hydrolase#Retaining_glycoside_hydrolases Retaining Glycoside Hydrolases]

===References===
<references/>

Hen Egg-White (HEW) Lysozyme

2011-04-20T18:28:05Z

Anne Goodling:

'''Introduction'''

Lysozyme - also known as muramidase, or glycoside hydrolase - is a powerful enzyme of biological significance found in abundance in tears, saliva, and human milk. In humans, it is encoded in the ''LYZ'' gene. Although it is responsible for the initial digestion of starches in the mouth, it is most widely identified as a non-specific defense in gram positive bacteria and in many species of fungi. Due to its antibacterial effects, it is a strong component of the innate immune system, and is an important part of an infant's diet to ward off diarrheal diseases. Since it is a small, easily available, and highly stable protein containing only 129 amino acid residues, it has been subject to extensive research regarding its function and structure. Hen Egg White (HEW) Lysozyme is shown below.

===History===

Lysozyme is an enzyme known for its unique ability to degrade the polysaccharide architecture of many kinds of cell walls, normally for the purpose of protection against bacterial infection<ref>Lysozyme. 2010. Citizendium.org. http://en.citizendium.org/wiki/Lysozyme</ref>. Its effects were first noticed by Laschtschenko in 1909. It was officially characterized and termed “lysozyme” by Alexander Fleming, the same person credited for the accidental discovery of penicillin.
The characterization of lysozyme in 1922 by Alexander Fleming was providential in that the undertaken experiment related to the discovery of lysozyme was not geared toward any knowledge of such a protein as lysozyme <ref>Lysozyme. 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>. During the unrelated experiment, nasal drippings were inadvertently introduced to a petri dish containing a bacterial culture, which culture consequently exhibited the results of an as yet unknown enzymatic reaction. The observation of this unknown reaction led to further research on the components of this reaction as well as to the corresponding identification of the newfound "lysozyme." Fleming's discovery was complemented by David C. Phillips' 1965 description of the three-dimensional structure of lysozyme via a 200 pm resolution model obtained from X-ray crystallography <ref>Lysozyme, 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>. Phillips' work was especially groundbreaking since Phillips had managed to successfully elucidate the structure of an enzyme via X-ray crystallography - a feat that had never before been accomplished<ref>Bugg, T. 1997. An Introduction to Enzyme and Coenzyme Chemistry. Blackwell Science Ltd., Oxford </ref>. Phillips' research also led to the first sufficiently described enzymatic mechanism of catalytic action <ref>1967. Proc R Soc Lond B Bio 167 (1009): 389–401.</ref>. Thus, Phillips' elucidation of the function of lysozyme led Phillips to reach a more general conclusion on the diversity of enzymatic chemical action in relation to enzymatic structure. Clearly, the findings of Phillips as well as the more general historical development of the understanding of the structure and function of lysozyme have been paramount to the more general realm of enzyme chemistry.

[[Image:nag-nam2.jpg|thumb|left|350px|Lysozyme Cleavage Site]]
<ref>Image from: http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/proteins/lysozyme.htm</ref>

'''Function'''

Lysozyme is known for damaging bacterial cell walls by catalyzing the hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid (NAM) and N-acetyl-D-glucosamine (NAG) residues in peptidoglycan, and between N-acetyl-D-glucosamine residues in chitodextrins. In this way, lysozyme is efficient in lysing the cell walls of both bacteria and fungi. The location of cleavage for lysozyme on this architectural theme is the β(1-4) glycosidic linkage connecting the C1 carbon of NAM to the C4 carbon of NAG.

The particular substrate of preference for this cleavage type is a (NAG-NAM)₃ hexasaccharide, within which substrate occurs the
cleaving target glycosidic bond, NAM₄-β-O-NAG₅. The individual hexasaccharide binding units are designated A-F, with NAM₄-β-O-NAG₅ glycosidic bond cleavage preference corresponding to a D-E unit glycosidic bond cleavage preference.

= Enzymatic Activity of Lysozyme =

Enzymes are designed to attract and to bind specific substrates. The active site of and lysozyme and its specific ligands are described in the following sections

==Mechanistic Features==

'''Zymogen of Lysozyme: Enzymatic Precursor'''

Zymogens are inactive enzyme precursors. Enzymes are developed in an inactive way to prevent the enzyme from digesting the cell that produced it. This process also prevents the enzyme from becoming active in the wrong portion of the body. Lysozyme's zymogen, simply titled “pre-lysozyme,” was sequenced in 1977 by R D Palmiter, J Gagnon, L H Ericsson and K A Walsh, and has since been sequenced much more extensively.

[[Image:jrip.jpg|thumb|left|350px|Mechanism of Lysozyme]]
<ref>Image from: http://www.google.com/imgres?imgurl=http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/pics-and-strucs/lysozyme-mech.gif&imgrefurl=http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/proteins/lysozyme.htm&usg=__ormapG4XKg-tR5GrMSOdSMTV4vE=&h=603&w=801&sz=7&hl=en&start=17&zoom=1&tbnid=nvr9gvFrUILDkM:&tbnh=143&tbnw=189&prev=/images%3Fq%3DThe%2Blysozyme%2Breaction%2Bmechanism%26um%3D1%26hl%3Den%26sa%3DN%26biw%3D1280%26bih%3D647%26tbs%3Disch:10%2C304&um=1&itbs=1&iact=hc&vpx=521&vpy=349&dur=448&hovh=191&hovw=254&tx=140&ty=48&ei=JQ_LTPKzLIjCsAPkzt2KDg&oei=IA_LTP74OsG78gapm-GFAQ&esq=2&page=2&ndsp=18&ved=1t:429,r:2,s:17&biw=1280&bih=647</ref>

'''Mechanism'''

The lysozyme mechanism of action results in the hydrolysis of a glycoside (hence the familial distinction of lysozyme as a glycosylase<ref>Lysozyme, 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>), which corresponds to the conversion of an acetal to a hemiacetal, which reaction (general degradation of glycosidic bond to units "capped" by newly formed hydroxyl groups) necessitates acid catalysis, since the conversion of acetal to hemiacetal involves the protonation of the reactant oxygen prior to actual bond cleavage. <ref>Pratt, C.W., Voet, D., Voet, J.G. Fundamentals of Biochemistry - Life at the Molecular Level - Third Edition. Voet, Voet and Pratt, 2008.</ref>. Furthermore, the transition state obtained from this protonation is a covalent, oxonium ion, intermediate that must obtain resonance stabilization. The need for some means of acid catalysis and covalent resonance stabilization is adequately provided by the Glu 35 and Asp 52 residues of lysozyme, respectively. The reaction mechanism of lysozyme is demonstrated below. In the following image, the reaction begins at the upper left-hand side, and proceeds according to reaction arrows.

As seen to the left, lysozyme works by hydrolyzing the glycosidic bond, distorting the bond between the NAM and NAG. This produces a glycosyl enzyme intermediate, which reacts with a water molecule to produce the product and the unchanged enzyme.

'''Active Site'''

The <scene name='Hen_Egg-White_(HEW)_Lysozyme/Act_site/2'>active site</scene> of lysozyme is formulated as a prominent cleft outlined by the two aforementioned catalytic amino acids, Glu 35 and Asp 52. The active site is geometrically bent to augment ligand binding, and the two amino acids interact with the ligand in the binding site. Asp52 is depicted in red, and Glu35 is depicted in green.

<applet load='1hew' size='350' frame='true' align='right' caption='' />

==Binding==
'''Ligands'''

A ligand is able to bind to the active site of an enzyme to form a biologically relevant complex. The model to the right shows a space-filling model of lysozyme with the protein distinguishable in brown and the ligand distinguishable in green. Another model of the ligand can be seen in this
<scene name='Hen_Egg-White_(HEW)_Lysozyme/Ligand/1'>ribbon diagram</scene>, with the ligand protruding as a space-filling model from the active site. Here, it is clear that the ligand is a polysaccharide.

The lysozyme reaction is characterized by hydrolysis of the beta (1-4) glycosidic bond between NAM and NAG. Lysozyme has a very specific active site, which can bind only six sugar rings from a polysaccharide chain. Once lysozyme binds to this chain, it hydrolyzes them. These six sugar rings represent the ligand of lysozyme. The lysozyme then distorts the fourth sugar in the six-membered complex, producing stress on the molecule and breaking the glycosidic bond.

The amino acid side-chains Glu35 and Asp52 are critical to the activity of this enzyme. Glu35 acts as a proton donor to the glycosidic bond, cleaving the C-O bond in the substrate, and Asp52 acts as a nucleophile to generate a glycosyl enzyme intermediate. The glycosyl enzyme intermediate then reacts with a water molecule to give the product of hydrolysis.

'''Inhibitors'''

Lysozyme is best inhibited by small saccharides which act competitively with the natural substrate. The smaller saccharides will bind to the first three binding sites of the cleft (sites A-C), but will not reach sites D and E, where the enzyme cuts the glycosidic bond. So, the competitive inhibitor will stick in the cleft, not allowing the substrate to bind to the enzyme complex.<ref>http://mcdb-webarchive.mcdb.ucsb.edu/sears/biochemistry/tw-enz/lysozyme/HEWL/lysozyme-overview.htm</ref> Several known inhibitors of lysozyme are: SDS, N-acetyl-D-glucosamine, and various alcohols and oxidizing agents.<ref>http://www.worthington-biochem.com/ly/default.html</ref>

<applet load='1hew' size='350' frame='true' align='left' caption='' />

= Composition and Structure of Lysozyme =

All proteins consist of carbon, hydrogen, nitrogen, oxygen, and sulfur, as do most organic molecules. Enzymes are composed in such a way as to maximize their reactivity with their desired substrate, increasing the efficiency of biological reactions. The <scene name='Sandbox_39/Elements/1'>composition of lysozyme</scene> can be seen on the left, with the carbon atoms outlined in gray, oxygen atoms in red, nitrogen atoms in blue, sulfur atoms in yellow, and the three-letter abbreviation for the <scene name='Sandbox_39/Amino_acid_residues/1'>amino acid residues</scene> in purple.

Lysozyme, like all proteins, also contains a <scene name='Sandbox_39/C_and_n_terminal_residues/1'> 3'C and 5'N terminal </scene>, and these can be seen by following the colors of the rainbow across the molecule. Starting at the red end, the 3' C terminal end, one can work the entire way through to the 5' N terminal end, showing the folding pattern and chain of the protein.

== Secondary Structure ==

Lysozyme contains five <scene name='Sandbox_38/A/2'>alpha helical</scene> regions and five regions containing <scene name='Sandbox_38/B/1'>beta sheets</scene> as displayed in this <scene name='Sandbox_38/Alphab/1'>image</scene>. Linking these secondary structures, a number of beta turns and a large number of random coils make up the remainder of the polypeptide backbone. The polypeptide backbone of lysozyme involved in the 3 antiparallel beta sheets display the beta hairpin motif of supersecondary structure. This depiction of lysozyme contains an antiparallel beta-pleated sheet, which contributes greatly to the stability of the molecule by providing the correct alignment of hydrogen bonds. Lysozyme also contains a great deal of random coil, which is seen in the white regions of the molecule.

==Amino Acid Residues==

The amino acids present in the lysozyme polypeptide sequence have a direct influence not only on primary structure, but also on the secondary and tertiary structures, which can be influenced by polarity and charge of the sidechains. The various amino acid <scene name='Sandbox_38/Aminoi/1'>residues sucky</scene>
<scene name='Hen_Egg-White_(HEW)_Lysozyme/Residue/1'>residues</scene>differ in their properties because of the great variety of side chains present on each amino acid. Polar and nonpolar (and charged and uncharged) side chains lead to various degrees of hydrophobicity and hydrophilicity, which affects protein folding. In lysozyme, these <scene name='Sandbox_38/Sc/1'>side chains</scene> are displayed for each amino acid residue.

= Bonding Interactions =

'''Disulfide Bonding in Lysozyme'''

Lysozyme contains four <scene name='Sandbox_39/Disulfide_bonds/1'>disulfide bonds</scene> involving eight cysteine residues, which are highlighted in yellow on the left. Disulfide bonds are intramolecular forces that stabilize the tertiary structure of many proteins. Disulfide bonds are present in four locations in lysozyme: between Cys 6 and Cys 127, between Cys 30 and Cys 115, between Cys 64 and Cys 80 and between Cys 76 and Cys 94.

'''Hydrogen Bonding'''

In all proteins <scene name='Sandbox_39/Hydrogen_bonds/2'>hydrogen bonds</scene> are essential for stability. In this ribbon diagram, the hydrogen bonds can be seen between the secondary structures of lysozyme highlighted in orange. Since the double bonds of the alpha carbons in the main chain of lysozyme cause torsional strain, lysozyme is limited to very specific hydrogen bonding between the amino acid residues. This representation clearly shows how crucial hydrogen bonding is to help maintain the stability of the protein.

<applet load='1hew' size='350' frame='true' align='left' caption='' />

= Intermolecular Interactions =

'''Hydrophobicity'''

Lysozyme contains both hydrophobic and hydrophilic regions ( <scene name='Sandbox_39/Hydrophobicity/2'>Hydrophobicity</scene> ). The hydrophilic effect, or the desire for proteins to be at a specific position regarding water, is the single most important determinant of protein folding. These regions can be displayed with the hydrophobic regions in gray and the polar, hydrophillic regions in purple. This coloration highlights the location of these regions, showing that the majority of the hydrophobic regions are inside of the protein and that the majority of the hydrophillic regions are on the outside of the protein.

'''Polarity'''

The nature of the amino acid sidechains in the lysozyme polypeptide sequence leads to regions of varying hydrophobicities and polarities of the enzyme structure. The presence of certain regions of hydrophilicity and hydrophobicity is a driving force in determining protein structure when folding. The varying polarities of the side chains influence the locations of residues in the enzyme structure. Nonpolar residues appear blue, and polar residues appear red in the following <scene name='Sandbox_38/Non_polar_blue/1'>polarity</scene> display of lysozyme. Nonpolar residues will display hydrophobic tendencies occurring mostly on the interior of the enzyme while polar residues will increase in abundance on the surface of the protein in order to increase contact with the aqueous solvent so as to satisfy their hydrophilic nature. By observing a space-filled structural depiction of <scene name='Sandbox_38/Non_polar_blu/1'>lysozyme polarity</scene> with polar molecules colored red and nonpolar molecules colored blue the influence of polarity on nucleotide arrangement and protein folding is evident, with the blue (nonpolar) regions inside the red (polar) regions. The presence of <scene name='Sandbox_39/Water/1'>water</scene> interacting with the various hydrophilic residues is depicted to further display how polarity affects structure. Water is depicted as yellow, and the polar and nonpolar regions remain their respective color.

'''Charge'''

Charges of the various regions of the lysozyme structure display a hydrophilic nature and thus also affect the location of that region of polypeptides and the overall folding of the protein. Charged regions of the protein will display hydrophilic tendencies and therefore will most often be located on the surface of the lysozyme molecule where they can interact with the aqueous solvent. Non-charged portions will display hydrophobic tendencies and be located on the interior of the molecule. The effect of various <scene name='Sandbox_38/Rb/1'>charges</scene> on protein structure can be visualized with charged molecules represented by red anionic and blue cationic regions, and uncharged regions colored in grey. This depiction of lysozyme uses a spacefill representation of lysozyme to depict <scene name='Sandbox_38/Chargeddd/1'>charges</scene>.

= Applications of Lysozyme =

Since lysozyme has been widely recognized for its antibacterial and antifungal properties, it has a wide variety of uses both in biochemical and pharmaceutical applications. In molecular biology, lysozyme is often used in the alkaline-lysis procedure for extracting and isolating plasmid DNA. It is used extensively in the pharmaceutical field for destroying gram-positive bacteria, and can be used to support already-existing immune defenses to fight bacterial infections. This enzyme is particularly important for preventing bacterial diseases in infants. Because of its antibacterial properties, lysozyme can also be used in the food industry to help prevent spoilage of foods.

= Discovery and Applications of Hen Egg-White Lysozyme=

<applet load='aln_1H6M_to_1HEW_2.pdb' size='300' frame='true' align='right' caption=' Hen Egg White (HEW) Lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to the active site, PDBid 1HEW' scene='User:Judy_Voet/Lysozyme/Lysozyme1/16' />
Lysozyme was the first enzyme whose X-ray structure was determined <ref> PMID 5840126</ref><ref>Phillips, D. C. The hen egg white lysozyme molecule. Proc. Natl Acad. Sci. USA 57, 483-495 (1967)</ref>. This <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>scene </scene> shows Hen Egg White (HEW) lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to a cleft in the enzyme. David Phillips, who determined the structure in 1965, saw that the cleft was large enough to fit three more saccharide units.
He therefore built a model extending the trisaccharide to a
<scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> that fits into the cleft, labeling the sugar subsites A-F<ref> coordinates of the model kindly provided by Louise Johnson</ref>. Alternately click on <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>trisaccharide</scene> and <scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> to turn the modeled portion of the hexasaccharide on and off.

The interesting thing about the model was that the only way that the hexasaccharide would fit into the cleft was if the 4th saccharide (in subsite D) was strained into a <scene name='User:Judy_Voet/Lysozyme/Half-chair/2'>half-chair conformation</scene>. This conformation is what would be necessary for the formation of an oxocarbenium ion (oxionium ion). When the model was studied, <scene name='User:Judy_Voet/Lysozyme/Glu_35/1'>Glu 35</scene> was found to be in an ideal location to act as a general acid catalyst, 3.34 Angstroms from the bridging oxygen between the 4th and 5th saccharide units. <scene name='User:Judy_Voet/Lysozyme/Asp_52/2'>Asp 52</scene> appeared to be too far away (2.69 angstroms) in the static lysozyme structure to have formed a covalent bond with C1 of the half-chair model in the D site, and no covalent intermediate had ever been detected, so Phillips proposed that it acted as an electrostatic stabilizer of the oxonium ion (referred to as The Phillips Mechanism).

<applet load='aln_1H6M_to_1HEW_2.pdb' size='200' frame='true' align='left' caption='NAG-2-deoxy-2-fluoro-glucosyl fluoride (NAG2FGlcF) bound to Glu35Gln HEW Lysozyme PDBid 1H6M' scene='User:Judy_Voet/Lysozyme/1h6m/3'/>

Then, in 2001, Stephen Withers published <scene name='User:Judy_Voet/Lysozyme/1h6m/3'>1H6M</scene>,<ref>PMID 11518970</ref> in which Glu 35 had been mutated to Gln to remove the general acid catalyst. The substrate contained NAG-2-fluoro-glucosyl fluoride (NAG2FGlcF). The fluoro group on C-1 does not require acid catalysis to be a good leaving group, and the remaining saccharide, in the absence of the acid necessary to catalyse the second step of the reaction, was demonstrated to form a <scene name='User:Judy_Voet/Lysozyme/Covalent/1'> covalent intermediate</scene>. In this <scene name='User:Judy_Voet/Lysozyme/Superposition/2'>superposition</scene> of the half chair model with 1HEW (greens) and the covalent intermediate in 1H6M (blues), note the relatively small motions of Asp 52 and C1 of the sugar ring in going from the model to the covalent intermediate. to observe the motion from the <scene name='User:Judy_Voet/Lysozyme/Asp52_halfchair/1'>half-chair</scene> to the <scene name='User:Judy_Voet/Lysozyme/Covalent/2'>covalent intermediate</scene> just toggle between the two green links.

== 3D Structures of Lysozyme ==

===Lys===

[[2x0a]], [[3iju]], [[3ijv]], [[3a8z]], [[2w1y]], [[2w1m]], [[2w1x]], [[2w1l]], [[3e3d]], [[3exd]], [[2zq3]], [[2zq4]], [[3b72]], [[3b6l]], [[2z12]], [[2z18]], [[2z19]], [[2vb1]], [[2hu3]], [[2hub]], [[2htx]], [[2hu1]], [[2yvb]], [[2epe]], [[2g4p]], [[2g4q]], [[2cgi]], [[2b5z]], [[2d4k]], [[2d91]], [[2f2n]], [[2fbb]], [[2c8o]], [[2c8p]], [[2a6u]], [[2aub]], [[2blx]], [[2bly]], [[2a7d]], [[2a7f]], [[1wtm]], [[1wtn]], [[1w6z]], [[1vdp]], [[1vdq]], [[1vds]], [[1vdt]], [[1ved]], [[1v7t]], [[1ps5]], [[2cds]], [[1lj3]], [[1lj4]], [[1lje]], [[1ljf]], [[1ljg]], [[1ljh]], [[1lji]], [[1ljj]], [[1ljk]], [[1jis]], [[1jit]], [[1jiy]], [[1jj0]], [[1jj1]], [[1jj3]], [[1iee]], [[1qio]], [[1f0w]], [[1f10]], [[1dpx]], [[1c10]], [[1qtk]], [[1lz8]], [[1lz9]], [[1bhz]], [[1bgi]], [[1bwh]], [[1bwi]], [[1bwj]], [[1bvx]], [[1hsw]], [[1hsx]], [[1lpi]], [[4lzt]], [[3lzt]], [[1aki]], [[1jpo]], [[1rfp]], [[193l]], [[194l]], [[5lym]], [[1lza]], [[3lyt]], [[4lyt]], [[5lyt]], [[6lyt]], [[2lzt]], [[1lzt]], [[1lzh]], [[2lzh]], [[7lyz]], [[1lyz]], [[2lyz]], [[3lyz]], [[4lyz]], [[5lyz]], [[6lyz]] - HEWL – chicken 
[[1xei]], [[1xej]], [[1xek]], [[1uco]], [[1lma]], [[4lym]] – HEWL low hydration 
[[1lsa]], [[1lsb]], [[1lsc]], [[1lsd]], [[1lse]], [[1lsf]], [[1lys]] – HEWL temperature influence 
[[2lym]], [[3lym]] – HEWL pressure influence 
[[132l]] – HEWL methylated 
[[1rcm]] – HEWL 3 S-S form 
[[2xbr]], [[2xbs]]- HEWL– Raman crystallography 
[[2zwb]], [[1io5]], [[1lzn]] - HEWL– Neutron 
[[1gxv]], [[1gxx]], [[1e8l]] - HEWL- NMR 
[[2hs7]], [[2hso]], [[2hs9]]- HEWL– Powder diffraction 
[[1ir7]], [[1ir8]], [[1ir9]], [[1ioq]], [[1ior]], [[1ios]], [[1iot]], [[1flq]], [[1flu]], [[1flw]], [[1fly]], [[1fn5]], [[1kxw]], [[1kxx]], [[1kxy]], [[1uia]], [[1uib]], [[1uic]], [[1uid]], [[1uie]], [[1uif]], [[1uig]], [[1uih]], [[1lsm]], [[1lsn]], [[1hel]], [[1hem]], [[1hen]], [[1heo]], [[1hep]], [[1heq]], [[1her]] – HEWL (mutant) 
[[1lyo]], [[2lyo]], [[3lyo]], [[4lyo]] – HEWL cross-linked 
[[1xft]] - tuLys – turkey - Powder diffraction 
[[1jse]], [[1tew]], [[135l]], [[2lz2]], [[1lz2]] – tuLys 
[[3lz2]] – tuLys - Laue 
[[3ab6]] – Lys + NAG3 – Hard clam 
[[2x8r]] – Lys GH25 – ''Aspergillus fumigatus'' 
[[3mgw]] – Lys G – Atlantic salmon 
[[3gxk]], [[3gxr]] – Lys G + NAG – Atlantic cod 
[[2fbd]] – HfLys 1 
[[3cb7]] – HfLys 2 
[[2zij]], [[2zik]], [[2zil]], [[2nwd]], [[1iwt]], [[1iwu]], [[1iwv]], [[1iww]], [[1iwx]], [[1iwy]], [[1iwz]], [[1jwr]], [[1jsf]], [[1rex]], [[1lz1]] – hLys – human 
[[1w08]], [[1ix0]], [[1ioc]], [[1ip1]], [[1ip2]], [[1ip3]], [[1ip4]], [[1ip5]], [[1ip6]], [[1ip7]], [[1qsw]], [[1gev]], [[1gez]], [[1gf0]], [[1gf3]], [[1gf4]], [[1gf5]], [[1gf6]], [[1gf7]], [[1i1z]], [[1i20]], [[1i22]], [[1gfr]], [[1gft]], [[1gfu]], [[1gfv]], [[1gf8]], [[1gf9]], [[1gfa]], [[1gfe]], [[1gfg]], [[1gfh]], [[1gfj]], [[1gfk]], [[1inu]], [[1gdx]], [[1ge0]], [[1ge1]], [[1ge2]], [[1ge3]], [[1ge4]], [[1gdw]], [[1gaz]], [[1gb0]], [[1gb2]], [[1gb3]], [[1gb5]], [[1gb6]], [[1gb7]], [[1gb8]], [[1gb9]], [[1gbo]], [[1gbw]], [[1gbx]], [[1gby]], [[1gbz]], [[1gay]], [[1eq4]], [[1eq5]], [[1eqe]], [[1c7p]], [[1di3]], [[1di4]], [[1di5]], [[1c43]], [[1c45]], [[1c46]], [[1ckg]], [[1cj6]], [[1cj7]], [[1cj8]], [[1cj9]], [[1ckc]], [[1ckd]], [[1ckf]], [[1ckh]], [[1b5z]], [[1b70]], [[1b7q]], [[1b7r]], [[1b7s]], [[1b7l]], [[1b7m]], [[1b7n]], [[1b7p]], [[1b5u]], [[1b5v]], [[1b5w]], [[1b5x]], [[1b5y]], [[1bb3]], [[1bb4]], [[2bqa]], [[2bqb]], [[2bqc]], [[2bqd]], [[2bqe]], [[2bqf]], [[2bqg]], [[2bqh]], [[2bqi]], [[2bqj]], [[2bqk]], [[2bql]], [[2bqm]], [[2bqn]], [[2bqo]], [[2mea]], [[2meb]], [[2mec]], [[2med]], [[2mee]], [[2mef]], [[2meg]], [[2meh]], [[2mei]], [[1wqm]], [[1wqn]], [[1wqo]], [[1wqp]], [[1wqq]], [[1wqr]], [[2heb]], [[2hea]], [[2hec]], [[2hed]], [[2hee]], [[2hef]], [[1jka]], [[1jkb]], [[1jkc]], [[1jkd]], [[1loz]], [[1lyy]], [[1oua]], [[1oub]], [[1ouc]], [[1oud]], [[1oue]], [[1ouf]], [[1oug]], [[1ouh]], [[1oui]], [[1ouj]], [[207l]], [[208l ]], [[1yam]], [[1yan]], [[1yao]], [[1yap]], [[1yaq]], [[1lmt]], [[1lhh]], [[1lhi]], [[1lhj]], [[1lhk]], [[1lhl]], [[133l]], [[134l]], [[1lz4]], [[1lz5]], [[1lz6]], [[1laa]], [[1tay]], [[1tby]], [[1tcy]], [[1tdy]], [[2lhm]], [[3lhm]] – hLys (mutant) 
[[1iy3]], [[1iy4]] – hLys - NMR 
[[2z2f]] – Lys – Bovine 
[[2cwi]], [[1el1]], [[1qqy]] – dLys - dog 
[[2z2e]] – dLys (mutant) 
[[1i56]] – dLys – NMR 
[[2dqa]] – Lys – ''Tapes japonica'' 
[[2gv0]] – Lys – Soft-shelled turtle 
[[1ivm]] – mLys M – NMR – mouse 
[[1jfx]] – Lys – ''Streptomyces coelicolor'' 
[[1gd6]] – Lys – ''Bombyx mori'' 
[[1jug]] – Lys – Echidna 
[[1dkj]] – BqLys – Bobwhite quail 
[[2ihl]] – Lys – Japanese quail 
[[1gbs]] – BsLys – Black swan 
[[1lmn]] – RtLys – Rainbow trout 
[[2eql]] – Lys – horse 
[[1ghl]] – phLys – pheasant 
[[1hhl]] – GfLys – Guinea fowl 
[[1lhm]] – Lys (mutant) – yeast 

===Lys small molecules complexes===

[[3fe0]], [[2d4i]], [[2d4j]], [[1v7s]] - HEWL+ D2O 
[[3m3u]] – HEWL Trp fluorescence 
[[2xjw]] - HEWL + CO 
[[1hf4]], [[1lks]] – HEWL + NO3 
[[3a34]], [[3ems]] - HEWL + arginine 
[[2xth]] – cLys + inhibitor K2PtBr6 
[[3a90]], [[3a91]], [[3a92]], [[3a93]], [[3a94]], [[3a95]], [[3a96]], [[3kam]], [[2pc2]], [[2bpu]], [[1t3p]], [[1h87]] – HEWL + rare earth 
[[2d6b]], [[2hg0]], [[1vat]], [[1gwd]], [[1b2k]], [[1lkr]], [[1azf]], [[8lyz]]- HEWL+ halogen 
[[1vat]] - HEWL + Xe 
[[1n4f]] - HEWL + As 
[[2i6z]] - HEWL + Pt drug 
[[2zyp]] - HEWL + poly (allyl amine) 
[[2f30]], [[2f4a]] – HEWL + urea derivative 
[[2f4g]], [[1ykx]], [[1yky]], [[1ykz]], [[1yl0]], [[1yl1]], [[1z55]] - HEWL + alcohol 
[[1dpw]] – HEWL + MPD 
[[1lcn]] – HEWL + SCN 
[[2zxs]] - HEWL with glycine-amide 
[[2h9j]], [[2h9k]], [[1yik]], [[1yil]] - HEWL + cyclam derivative 
[[1b0d]] – HEWL + p-toluene-sulfonate 
[[2q0m]] - HEWL + tricarbonylmanganese 
[[2war]] – HEWL (mutant) + chitopentaose 
[[2h5z]] – HfLys 1 + chitotetraose – House fly 
[[1hnl]] – hLys + glutathione 
[[1dkk]] – BqLys + NO3 

===Lys complex with glucoside===

[[3a3q]] – HEWL (mutant) + NAG 
[[1sf4]], [[1sf6]], [[1sf7]], [[1sfb]], [[1sfg]], [[1ja2]], [[1ja4]], [[1ja6]], [[1ja7]] – HEWL + NAG oligosaccharide – Powder diffraction 
[[1ubz]], [[1d6p]], [[1d6q]], [[1bb5]] – hLys (mutant) + glycoside 
[[1uc0]], [[1re2]], [[1rem]], [[1rey]], [[1rez]], [[1lzr]], [[1lzs]] - hLys + glycoside 
[[1ljn]], [[1jef]], [[1lzy]] – tuLys + glycoside 
[[1h6m]], [[1at5]], [[1at6]], [[1lzb]], [[1lzc]], [[1lzd]], [[1lze]], [[1lzg]], [[1hew ]]– HEWL + glycoside 
[[1lsy]], [[1lsz]] - HEWL (mutant) + glycoside 
[[1bb6]], [[1bb7]] – RtLys + glycoside 
[[1lmc]] – RtLys + bulgecin 
[[1lmo]], [[1lmp]], [[1lmq]] – RtLys + glucoside 
[[1lsp]] – BsLys + bulgecin 
[[153l]], [[154l]] – Lys +glucoside – goose 

===Phage Lys===

[[2oe4]], [[2oe7]], [[2oe9]], [[2oea]], [[1swz]], [[1cx6]], [[1qtc]], [[1qtd]], [[1qth]], [[1qsb]], [[1qs5]], [[1qs9]], [[1qtb]], [[256l]], [[206l]], [[167l]], [[168l]], [[169l]], [[170l]], [[171l]], [[172l]], [[173l]], [[174l]], [[175l]], [[176l]], [[177l]], [[178l]], [[181l]], [[182l]], [[183l]], [[184l]], [[185l]], [[186l]], [[187l]], [[188l]], [[1nhb]], [[137l]], [[216l]], [[152l]], [[149l]], [[150l]], [[151l]], [[1lyd]], [[2lzm]] - T4Lys – Enterobacteria phage T4 
[[138l]] – T4Lys cross-linked 
[[4lzm]], [[5lzm]], [[6lzm]], [[7lzm]] – T4Lys ionic strength 
[[3l2x]], [[3k2r]], [[3g3v]], [[3g3w]], [[3g3x]], [[2q9d]], [[2q9e]], [[2igc]], [[2ntg]], [[2nth]], [[2ou8]], [[2ou9]], [[1zur]], [[1zwn]], [[1zyt]], [[2cuu]], [[2a4t]] – T4Lys (mutant) spin labeled 
[[3l64]], [[3hwl]], [[3jr6]], [[3gui]], [[3c7w]], [[3c7y]], [[3c7z]], [[3c80]], [[3c81]], [[3c82]], [[3c83]], [[3c8q]], [[3c8r]], [[3c8s]], [[3cdo]], [[3cdq]], [[3cdr]], [[3cdt]], [[3cdv]], [[3f8v]], [[3f9l]], [[3fa0]], [[3fad]], [[3fi5]], [[3dke]], [[3dmv]], [[2o4w]], [[2o79]], [[2o7a]], [[2huk]], [[2hul]], [[2hum]], [[2b7x]], [[2b6t]], [[2b6w]], [[2b6x]], [[2b6y]], [[2b6z]], [[2b70]], [[2b72]], [[2b73]], [[2b74]], [[2b75]], [[1sx7]], [[1swy]], [[1sx2]], [[1t6h]], [[1ssw]], [[1ssy]], [[1t8f]], [[1t8g]], [[1t8a]], [[1t97]], [[1p56]], [[1p5c]], [[1p2l]], [[1p2r]], [[1p36]], [[1p37]], [[1p3n]], [[1p46]], [[1p64]], [[1p6y]], [[1p7s]], [[1pqd]], [[1pqi]], [[1pqj]], [[1pqk]], [[1pqm]], [[1pqo]], [[1oyu]], [[1ks3]], [[1kw5]], [[1kw7]], [[1ky0]], [[1ky1]], [[1l0j]], [[1l0k]], [[1lw9]], [[1lwg]], [[1lwk]], [[1lpy]], [[1llh]], [[1lgu]], [[1li6]], [[1jtm]], [[1jtn]], [[1jqu]], [[1kni]], [[1g06]], [[1g07]], [[1g0g]], [[1g0j]], [[1g0k]], [[1g0l]], [[1g0m]], [[1g0p]], [[1g0q]], [[1g1v]], [[1g1w]], [[1i6s]], [[257l]], [[258l]], [[260l]], [[1epy]], [[1b6i]], [[1cu6]], [[1d9w]], [[1ctw]], [[1cu0]], [[1cu2]], [[1cu3]], [[1cu5]], [[1cv1]], [[1cv4]], [[1cv5]], [[1cv6]], [[1cvk]], [[1cx7]], [[1d2w]], [[1d2y]], [[1d3f]], [[1d3j]], [[1d3m]], [[1d3n]], [[1cv3]], [[1qt3]], [[1qt4]], [[1qt5]], [[1qt6]], [[1qt7]], [[1qt8]], [[1qtv]], [[1qtz]], [[1qud]], [[1qug]], [[1quh]], [[1quo]], [[1qsq]], [[261l]], [[262l]], [[259l]], [[220l]], [[222l]], [[223l]], [[225l]], [[226l]], [[227l]], [[228l]], [[229l]], [[235l]], [[236l]], [[237l]], [[238l]], [[239l]], [[240l]], [[241l]], [[242l]], [[243l]], [[244l]], [[245l]], [[246l]], [[247l]], [[248l]], [[249l]], [[250l]], [[251l]], [[252l]], [[253l]], [[254l]], [[255l]], [[230l]], [[231l]], [[232l]], [[233l]], [[234l]], [[209l]], [[210l]], [[211l]], [[212l]], [[213l]], [[214l]], [[215l]], [[218l]], [[219l]], [[180l]], [[195l]], [[196l]], [[197l]], [[198l]], [[199l]], [[200l]], [[190l]], [[191l]], [[192l]], [[189l]], [[155l]], [[156l]], [[157l]], [[158l]], [[159l]], [[160l]], [[161l]], [[162l]], [[163l]], [[164l]], [[165l]], [[166l]], [[129l]], [[130l]], [[131l]], [[140l]], [[141l]], [[142l]], [[143l]], [[144l]], [[145l]], [[146l]], [[147l]], [[201l]], [[205l]], [[221l]], [[224l]], [[102l]], [[103l]], [[104l]], [[107l]], [[108l]], [[109l]], [[110l]], [[111l]], [[112l]], [[113l]], [[114l]], [[115l]], [[118l]], [[119l]], [[120l]], [[122l]], [[123l]], [[125l]], [[126l]], [[127l]], [[128l]], [[1dya]], [[1dyb]], [[1dyc]], [[1dyd]], [[1dye]], [[1dyf]], [[1dyg]], [[1l00]], [[1l85]], [[1l86]], [[1l87]], [[1l88]], [[1l89]], [[1l90]], [[1l91]], [[1l92]], [[1l93]], [[1l94]], [[1l95]], [[1l96]], [[1l97]], [[1l98]], [[1l99]], [[1lye]], [[1lyf]], [[1lyg]], [[1lyh]], [[1lyi]], [[1lyj]], [[217l]], [[1tla]], [[1l77]], [[1l79]], [[1l80]], [[1l81]], [[1l82]], [[2l78]], [[1l36]], [[1l37]], [[1l38]], [[1l39]], [[1l40]], [[1l41]], [[1l42]], [[1l43]], [[1l44]], [[1l45]], [[1l46]], [[1l47]], [[1l48]], [[1l49]], [[1l50]], [[1l51]], [[1l52]], [[1l53]], [[1l54]], [[1l55]], [[1l56]], [[1l57]], [[1l58]], [[1l59]], [[1l60]], [[1l61]], [[1l62]], [[1l63]], [[1l64]], [[1l65]], [[1l66]], [[1l67]], [[1l68]], [[1l69]], [[1l70]], [[1l71]], [[1l72]], [[1l73]], [[1l74]], [[1l75]], [[1l76]], [[1l17]], [[1l18]], [[1l19]], [[1l20]], [[1l21]], [[1l22]], [[1l23]], [[1l24]], [[1l25]], [[1l26]], [[1l27]], [[1l28]], [[1l29]], [[1l30]], [[1l31]], [[1l32]], [[1l33]], [[1l34]], [[1l35]], [[3lzm]], [[1l01]], [[1l02]], [[1l03]], [[1l04]], [[1l05]], [[1l06]], [[1l07]], [[1l08]], [[1l09]], [[1l10]], [[1l11]], [[1l12]], [[1l13]], [[1l14]], [[1l15]], [[1l16]] – T4Lys (mutant) 
[[1c60]], [[1c61]], [[1c62]], [[1c63]], [[1c64]], [[1c65]], [[1c66]], [[1c67]], [[1c68]], [[1c69]], [[1c6a]], [[1c6b]], [[1c6c]], [[1c6d]], [[1c6e]], [[1c6f]], [[1c6g]], [[1c6h]], [[1c6i]], [[1c6j]], [[1c6k]], [[1c6l]], [[1c6m]], [[1c6n]], [[1c6p]], [[1c6q]], [[1c6t]] - T4Lys (mutant) + noble gas 
[[3ht6]], [[3ht7]], [[3ht8]], [[3ht9]], [[3htb]], [[3hu8]], [[3huq]], [[3guj]], [[3guk]], [[3gul]], [[3gum]], [[3gun]], [[3guo]], [[3gup]], [[3dmx]], [[3dmz]], [[3dn0]], [[3dn1]], [[3dn2]], [[3dn3]], [[3dn4]], [[3dn6]], [[3dn8]], [[3dna]], [[2rb1]], [[2ray]], [[2raz]], [[2rb0]], [[2rb2]], [[2rbn]], [[2rbo]], [[2rbq]], [[2rbr]], [[2rbs]], [[2oty]],[[2otz]], [[1owy]], [[1owz]], [[1ov5]], [[1ov7]], [[1ovh]], [[1ovj]], [[1ovk]], [[1lgw]], [[1lgx]], [[1li2]], [[1li3]], [[1l83]], [[1l84]] – T4Lys (mutant) + benzene derivative 
[[3htd]], [[3htf]], [[3htg]], [[3hu9]], [[3hua]], [[3huk]], [[3hh3]], [[3hh4]], [[3hh5]], [[3hh6]], [[2rbp]], [[2ou0]], [[2f2q]], [[2f32]], [[2f47]], [[1xep]] – T4Lys (mutant) + inhibitor 
[[148l]] - T4Lys (mutant) + glucoside 
[[3d3d]], [[1d9u]] – lamLys + chitohexasaccharide 
[[1am7]] – lamLys - Enterobacteria phage λ 
[[2anv]], [[2anx]] – Lys (mutant)]] - Enterobacteria phage p22 
[[1xjt]], [[1xju]] - Lys - Enterobacteria phage p1 
[[1lba]] - T7Lys - Enterobacteria phage T7 

===Lys protein complex===

[[3m18]], [[3g3a]], [[3g3b]] - HEWL + Variable lymphocyte receptor – Marine lamprey 
[[3a67]], [[3a6b]], [[3a6c]], [[2yss]], [[2eiz]], [[2dqc]], [[2dqd]], [[2dqe]], [[2dqf]], [[2dqg]], [[2dqh]], [[2dqi]], [[2dqj]], [[1j1o]], [[1j1p]], [[1j1x]], [[1ic4]], [[1ic5]], [[1ic7]] – HEWL + mLys antibody HYHEL-10 (mutant) 
[[1xgp]], [[1xgq]], [[1xgr]], [[1xgt]], [[1xgu]] – HEWL + mLys antibody HYHEL-63 
[[3d9a]], [[2eks]], [[1ua6]], [[1c08]], [[3hfm]] – HEWL + mLys antibody HYHEL-10 
[[1uac]] - tuLys C + mLys antibody HYHEL-10 
[[1yqv]], [[2iff]] – HEWL + mLys antibody HYHEL-5 
[[1bql]] – BqLys + mLys antibody HYHEL-5 
[[1ndg]] – HEWL + mLys antibody HYHEL-8 
[[1ndm]] – HEWL + mLys antibody HYHEL-26 
[[1dqj]] - HEWL + mLys antibody HYHEL-63 
[[1nby]], [[1nbz]] – HEWL (mutant) + mLys antibody HYHEL-63 
[[1g7h]], [[1g7i]], [[1g7j]], [[1g7l]], [[1g7m]], [[1kip]], [[1kiq]], [[1kir]] – HEWL + mAnti-HEWL monoclonal antibody (mutant) 
[[1mlc]], [[1vfb]] - HEWL + mIGG1-κ D44.1 FAB 
[[1a2y]] - HEWL (mutant) + mIGG1-κ D1.3 FV 
[[1fdl]] - HEWL + mIGG1-κ D1.3 FAB 
[[1jhl]] – phLys + mIGG1-κ D11.15 FV 
[[1fbi]] – GfLys + mIGG1 F9.13.7 FAB 
[[2znw]], [[2znx]] – HEWL + hSCFV10 antibody 
[[1bvk]] - HEWL + hAnti Lys FV antibody 
[[1dzb]] – tuLys + mSCFV 1F9 
[[1zv5]], [[1zvh]], [[1zvy]], [[1zmy]], [[1ri8]], [[1rjc]], [[1xfp]], [[1jtp]], [[1jtt]], [[1jto]], [[1mel]] - HEWL + cAntibody heavy chain domain – camel 
[[1op9]] - hLys C + cAntibody heavy chain domain 
[[3otp]] – HEWL + EcProtease DO – ''Escherichia coli'' 
[[3f6z]] - HEWL + MLIC – ''Pseudomonas aeruginosa'' 
[[3eba]] – hLys C + hCABHUL6 
[[2qb0]], [[2qar]] – T4Lys/E80 TELSAM domain 
[[2i25]], [[2i26]] - HEWL +NsAntigen receptor PBLA8 variable domain – Nurse shark 
[[1sq2]], [[1t6v]] – HEWL +NsNew Antigen receptor variable domain 
[[1gpq]] – HEWL + EcInhibitor of Vertebrate Lys 
[[1aro]] – T7Lys + T7 RNA polymerase 

===Some Useful External Links===
[http://en.wikipedia.org/wiki/Lysozyme Lysozyme]

[http://en.wikipedia.org/wiki/Glycoside_hydrolase#Retaining_glycoside_hydrolases Retaining Glycoside Hydrolases]

===References===
<references/>

Hen Egg-White (HEW) Lysozyme

2011-04-20T18:10:20Z

Anne Goodling:

'''Introduction'''

Lysozyme - also known as muramidase, or glycoside hydrolase - is a powerful enzyme of biological significance found in abundance in tears, saliva, and human milk. In humans, it is encoded in the ''LYZ'' gene. Although it is responsible for the initial digestion of starches in the mouth, it is most widely identified as a non-specific defense in gram positive bacteria and in many species of fungi. Due to its antibacterial effects, it is a strong component of the innate immune system, and is an important part of an infant's diet to ward off diarrheal diseases. Since it is a small, easily available, and highly stable protein containing only 129 amino acid residues, it has been subject to extensive research regarding its function and structure. Hen Egg White (HEW) Lysozyme is shown below.

===History===

Lysozyme is an enzyme known for its unique ability to degrade the polysaccharide architecture of many kinds of cell walls, normally for the purpose of protection against bacterial infection<ref>Lysozyme. 2010. Citizendium.org. http://en.citizendium.org/wiki/Lysozyme</ref>. Its effects were first noticed by Laschtschenko in 1909. It was officially characterized and termed “lysozyme” by Alexander Fleming, the same person credited for the accidental discovery of penicillin.
The characterization of lysozyme in 1922 by Alexander Fleming was providential in that the undertaken experiment related to the discovery of lysozyme was not geared toward any knowledge of such a protein as lysozyme <ref>Lysozyme. 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>. During the unrelated experiment, nasal drippings were inadvertently introduced to a petri dish containing a bacterial culture, which culture consequently exhibited the results of an as yet unknown enzymatic reaction. The observation of this unknown reaction led to further research on the components of this reaction as well as to the corresponding identification of the newfound "lysozyme." Fleming's discovery was complemented by David C. Phillips' 1965 description of the three-dimensional structure of lysozyme via a 200 pm resolution model obtained from X-ray crystallography <ref>Lysozyme, 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>. Phillips' work was especially groundbreaking since Phillips had managed to successfully elucidate the structure of an enzyme via X-ray crystallography - a feat that had never before been accomplished<ref>Bugg, T. 1997. An Introduction to Enzyme and Coenzyme Chemistry. Blackwell Science Ltd., Oxford </ref>. Phillips' research also led to the first sufficiently described enzymatic mechanism of catalytic action <ref>1967. Proc R Soc Lond B Bio 167 (1009): 389–401.</ref>. Thus, Phillips' elucidation of the function of lysozyme led Phillips to reach a more general conclusion on the diversity of enzymatic chemical action in relation to enzymatic structure. Clearly, the findings of Phillips as well as the more general historical development of the understanding of the structure and function of lysozyme have been paramount to the more general realm of enzyme chemistry.

[[Image:nag-nam2.jpg|thumb|left|350px|Lysozyme Cleavage Site]]
<ref>Image from: http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/proteins/lysozyme.htm</ref>

'''Function'''

Lysozyme is known for damaging bacterial cell walls by catalyzing the hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid (NAM) and N-acetyl-D-glucosamine (NAG) residues in peptidoglycan, and between N-acetyl-D-glucosamine residues in chitodextrins. In this way, lysozyme is efficient in lysing the cell walls of both bacteria and fungi. The location of cleavage for lysozyme on this architectural theme is the β(1-4) glycosidic linkage connecting the C1 carbon of NAM to the C4 carbon of NAG.

The particular substrate of preference for this cleavage type is a (NAG-NAM)₃ hexasaccharide, within which substrate occurs the
cleaving target glycosidic bond, NAM₄-β-O-NAG₅. The individual hexasaccharide binding units are designated A-F, with NAM₄-β-O-NAG₅ glycosidic bond cleavage preference corresponding to a D-E unit glycosidic bond cleavage preference.

= Enzymatic Activity of Lysozyme =

Enzymes are designed to attract and to bind specific substrates. The active site of and lysozyme and its specific ligands are described in the following sections

==Mechanistic Features==

'''Zymogen of Lysozyme: Enzymatic Precursor'''

Zymogens are inactive enzyme precursors. Enzymes are developed in an inactive way to prevent the enzyme from digesting the cell that produced it. This process also prevents the enzyme from becoming active in the wrong portion of the body. Lysozyme's zymogen, simply titled “pre-lysozyme,” was sequenced in 1977 by R D Palmiter, J Gagnon, L H Ericsson and K A Walsh, and has since been sequenced much more extensively.

[[Image:jrip.jpg|thumb|left|350px|Mechanism of Lysozyme]]
<ref>Image from: http://www.google.com/imgres?imgurl=http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/pics-and-strucs/lysozyme-mech.gif&imgrefurl=http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/proteins/lysozyme.htm&usg=__ormapG4XKg-tR5GrMSOdSMTV4vE=&h=603&w=801&sz=7&hl=en&start=17&zoom=1&tbnid=nvr9gvFrUILDkM:&tbnh=143&tbnw=189&prev=/images%3Fq%3DThe%2Blysozyme%2Breaction%2Bmechanism%26um%3D1%26hl%3Den%26sa%3DN%26biw%3D1280%26bih%3D647%26tbs%3Disch:10%2C304&um=1&itbs=1&iact=hc&vpx=521&vpy=349&dur=448&hovh=191&hovw=254&tx=140&ty=48&ei=JQ_LTPKzLIjCsAPkzt2KDg&oei=IA_LTP74OsG78gapm-GFAQ&esq=2&page=2&ndsp=18&ved=1t:429,r:2,s:17&biw=1280&bih=647</ref>

'''Mechanism'''

The lysozyme mechanism of action results in the hydrolysis of a glycoside (hence the familial distinction of lysozyme as a glycosylase<ref>Lysozyme, 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>), which corresponds to the conversion of an acetal to a hemiacetal, which reaction (general degradation of glycosidic bond to units "capped" by newly formed hydroxyl groups) necessitates acid catalysis, since the conversion of acetal to hemiacetal involves the protonation of the reactant oxygen prior to actual bond cleavage. <ref>Pratt, C.W., Voet, D., Voet, J.G. Fundamentals of Biochemistry - Life at the Molecular Level - Third Edition. Voet, Voet and Pratt, 2008.</ref>. Furthermore, the transition state obtained from this protonation is a covalent, oxonium ion, intermediate that must obtain resonance stabilization. The need for some means of acid catalysis and covalent resonance stabilization is adequately provided by the Glu 35 and Asp 52 residues of lysozyme, respectively. The reaction mechanism of lysozyme is demonstrated below. In the following image, the reaction begins at the upper left-hand side, and proceeds according to reaction arrows.

As seen to the left, lysozyme works by hydrolyzing the glycosidic bond, distorting the bond between the NAM and NAG. This produces a glycosyl enzyme intermediate, which reacts with a water molecule to produce the product and the unchanged enzyme.

'''Active Site'''

The <scene name='Hen_Egg-White_(HEW)_Lysozyme/Act_site/2'>active site</scene> of lysozyme is formulated as a prominent cleft outlined by the two aforementioned catalytic amino acids, Glu 35 and Asp 52. The active site is geometrically bent to augment ligand binding, and the two amino acids interact with the ligand in the binding site. Asp52 is depicted in red, and Glu35 is depicted in green.

<applet load='1hew' size='350' frame='true' align='right' caption='' />

==Binding==
'''Ligands'''

A ligand is able to bind to the active site of an enzyme to form a biologically relevant complex. The model to the right shows a space-filling model of lysozyme with the protein distinguishable in brown and the ligand distinguishable in green. Another model of the ligand can be seen in this
<scene name='Hen_Egg-White_(HEW)_Lysozyme/Ligand/1'>ribbon diagram</scene>, with the ligand protruding as a space-filling model from the active site. Here, it is clear that the ligand is a polysaccharide.

The lysozyme reaction is characterized by hydrolysis of the beta (1-4) glycosidic bond between NAM and NAG. Lysozyme has a very specific active site, which can bind only six sugar rings from a polysaccharide chain. Once lysozyme binds to this chain, it hydrolyzes them. These six sugar rings represent the ligand of lysozyme. The lysozyme then distorts the fourth sugar in the six-membered complex, producing stress on the molecule and breaking the glycosidic bond.

The amino acid side-chains Glu35 and Asp52 are critical to the activity of this enzyme. Glu35 acts as a proton donor to the glycosidic bond, cleaving the C-O bond in the substrate, and Asp52 acts as a nucleophile to generate a glycosyl enzyme intermediate. The glycosyl enzyme intermediate then reacts with a water molecule to give the product of hydrolysis.

'''Inhibitors'''

Lysozyme is best inhibited by small saccharides which act competitively with the natural substrate. The smaller saccharides will bind to the first three binding sites of the cleft (sites A-C), but will not reach sites D and E, where the enzyme cuts the glycosidic bond. So, the competitive inhibitor will stick in the cleft, not allowing the substrate to bind to the enzyme complex.<ref>http://mcdb-webarchive.mcdb.ucsb.edu/sears/biochemistry/tw-enz/lysozyme/HEWL/lysozyme-overview.htm</ref> Several known inhibitors of lysozyme are: SDS, N-acetyl-D-glucosamine, and various alcohols and oxidizing agents.<ref>http://www.worthington-biochem.com/ly/default.html</ref>

<applet load='1hew' size='350' frame='true' align='left' caption='' />

= Composition and Structure of Lysozyme =

All proteins consist of carbon, hydrogen, nitrogen, oxygen, and sulfur, as do most organic molecules. Enzymes are composed in such a way as to maximize their reactivity with their desired substrate, increasing the efficiency of biological reactions. The <scene name='Sandbox_39/Elements/1'>composition of lysozyme</scene> can be seen on the left, with the carbon atoms outlined in gray, oxygen atoms in red, nitrogen atoms in blue, sulfur atoms in yellow, and the three-letter abbreviation for the <scene name='Sandbox_39/Amino_acid_residues/1'>amino acid residues</scene> in purple.

Lysozyme, like all proteins, also contains a <scene name='Sandbox_39/C_and_n_terminal_residues/1'> 3'C and 5'N terminal </scene>, and these can be seen by following the colors of the rainbow across the molecule. Starting at the red end, the 3' C terminal end, one can work the entire way through to the 5' N terminal end, showing the folding pattern and chain of the protein.

== Secondary Structure ==

Lysozyme contains five <scene name='Sandbox_38/A/2'>alpha helical</scene> regions and five regions containing <scene name='Sandbox_38/B/1'>beta sheets</scene> as displayed in this <scene name='Sandbox_38/Alphab/1'>image</scene>. Linking these secondary structures, a number of beta turns and a large number of random coils make up the remainder of the polypeptide backbone. The polypeptide backbone of lysozyme involved in the 3 antiparallel beta sheets display the beta hairpin motif of supersecondary structure. This depiction of lysozyme contains an antiparallel beta-pleated sheet, which contributes greatly to the stability of the molecule by providing the correct alignment of hydrogen bonds. Lysozyme also contains a great deal of random coil, which is seen in the white regions of the molecule.

==Amino Acid Residues==

The amino acids present in the lysozyme polypeptide sequence have a direct influence not only on primary structure, but also on the secondary and tertiary structures, which can be influenced by polarity and charge of the sidechains. The various amino acid <scene name='Sandbox_38/Aminoi/1'>residues</scene> differ in their properties because of the great variety of side chains present on each amino acid. Polar and nonpolar (and charged and uncharged) side chains lead to various degrees of hydrophobicity and hydrophilicity, which affects protein folding. In lysozyme, these <scene name='Sandbox_38/Sc/1'>side chains</scene> are displayed for each amino acid residue.

= Bonding Interactions =

'''Disulfide Bonding in Lysozyme'''

Lysozyme contains four <scene name='Sandbox_39/Disulfide_bonds/1'>disulfide bonds</scene> involving eight cysteine residues, which are highlighted in yellow on the left. Disulfide bonds are intramolecular forces that stabilize the tertiary structure of many proteins. Disulfide bonds are present in four locations in lysozyme: between Cys 6 and Cys 127, between Cys 30 and Cys 115, between Cys 64 and Cys 80 and between Cys 76 and Cys 94.

'''Hydrogen Bonding'''

In all proteins <scene name='Sandbox_39/Hydrogen_bonds/2'>hydrogen bonds</scene> are essential for stability. In this ribbon diagram, the hydrogen bonds can be seen between the secondary structures of lysozyme highlighted in orange. Since the double bonds of the alpha carbons in the main chain of lysozyme cause torsional strain, lysozyme is limited to very specific hydrogen bonding between the amino acid residues. This representation clearly shows how crucial hydrogen bonding is to help maintain the stability of the protein.

<applet load='1hew' size='350' frame='true' align='left' caption='' />

= Intermolecular Interactions =

'''Hydrophobicity'''

Lysozyme contains both hydrophobic and hydrophilic regions ( <scene name='Sandbox_39/Hydrophobicity/2'>Hydrophobicity</scene> ). The hydrophilic effect, or the desire for proteins to be at a specific position regarding water, is the single most important determinant of protein folding. These regions can be displayed with the hydrophobic regions in gray and the polar, hydrophillic regions in purple. This coloration highlights the location of these regions, showing that the majority of the hydrophobic regions are inside of the protein and that the majority of the hydrophillic regions are on the outside of the protein.

'''Polarity'''

The nature of the amino acid sidechains in the lysozyme polypeptide sequence leads to regions of varying hydrophobicities and polarities of the enzyme structure. The presence of certain regions of hydrophilicity and hydrophobicity is a driving force in determining protein structure when folding. The varying polarities of the side chains influence the locations of residues in the enzyme structure. Nonpolar residues appear blue, and polar residues appear red in the following <scene name='Sandbox_38/Non_polar_blue/1'>polarity</scene> display of lysozyme. Nonpolar residues will display hydrophobic tendencies occurring mostly on the interior of the enzyme while polar residues will increase in abundance on the surface of the protein in order to increase contact with the aqueous solvent so as to satisfy their hydrophilic nature. By observing a space-filled structural depiction of <scene name='Sandbox_38/Non_polar_blu/1'>lysozyme polarity</scene> with polar molecules colored red and nonpolar molecules colored blue the influence of polarity on nucleotide arrangement and protein folding is evident, with the blue (nonpolar) regions inside the red (polar) regions. The presence of <scene name='Sandbox_39/Water/1'>water</scene> interacting with the various hydrophilic residues is depicted to further display how polarity affects structure. Water is depicted as yellow, and the polar and nonpolar regions remain their respective color.

'''Charge'''

Charges of the various regions of the lysozyme structure display a hydrophilic nature and thus also affect the location of that region of polypeptides and the overall folding of the protein. Charged regions of the protein will display hydrophilic tendencies and therefore will most often be located on the surface of the lysozyme molecule where they can interact with the aqueous solvent. Non-charged portions will display hydrophobic tendencies and be located on the interior of the molecule. The effect of various <scene name='Sandbox_38/Rb/1'>charges</scene> on protein structure can be visualized with charged molecules represented by red anionic and blue cationic regions, and uncharged regions colored in grey. This depiction of lysozyme uses a spacefill representation of lysozyme to depict <scene name='Sandbox_38/Chargeddd/1'>charges</scene>.

= Applications of Lysozyme =

Since lysozyme has been widely recognized for its antibacterial and antifungal properties, it has a wide variety of uses both in biochemical and pharmaceutical applications. In molecular biology, lysozyme is often used in the alkaline-lysis procedure for extracting and isolating plasmid DNA. It is used extensively in the pharmaceutical field for destroying gram-positive bacteria, and can be used to support already-existing immune defenses to fight bacterial infections. This enzyme is particularly important for preventing bacterial diseases in infants. Because of its antibacterial properties, lysozyme can also be used in the food industry to help prevent spoilage of foods.

= Discovery and Applications of Hen Egg-White Lysozyme=

<applet load='aln_1H6M_to_1HEW_2.pdb' size='300' frame='true' align='right' caption=' Hen Egg White (HEW) Lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to the active site, PDBid 1HEW' scene='User:Judy_Voet/Lysozyme/Lysozyme1/16' />
Lysozyme was the first enzyme whose X-ray structure was determined <ref> PMID 5840126</ref><ref>Phillips, D. C. The hen egg white lysozyme molecule. Proc. Natl Acad. Sci. USA 57, 483-495 (1967)</ref>. This <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>scene </scene> shows Hen Egg White (HEW) lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to a cleft in the enzyme. David Phillips, who determined the structure in 1965, saw that the cleft was large enough to fit three more saccharide units.
He therefore built a model extending the trisaccharide to a
<scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> that fits into the cleft, labeling the sugar subsites A-F<ref> coordinates of the model kindly provided by Louise Johnson</ref>. Alternately click on <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>trisaccharide</scene> and <scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> to turn the modeled portion of the hexasaccharide on and off.

The interesting thing about the model was that the only way that the hexasaccharide would fit into the cleft was if the 4th saccharide (in subsite D) was strained into a <scene name='User:Judy_Voet/Lysozyme/Half-chair/2'>half-chair conformation</scene>. This conformation is what would be necessary for the formation of an oxocarbenium ion (oxionium ion). When the model was studied, <scene name='User:Judy_Voet/Lysozyme/Glu_35/1'>Glu 35</scene> was found to be in an ideal location to act as a general acid catalyst, 3.34 Angstroms from the bridging oxygen between the 4th and 5th saccharide units. <scene name='User:Judy_Voet/Lysozyme/Asp_52/2'>Asp 52</scene> appeared to be too far away (2.69 angstroms) in the static lysozyme structure to have formed a covalent bond with C1 of the half-chair model in the D site, and no covalent intermediate had ever been detected, so Phillips proposed that it acted as an electrostatic stabilizer of the oxonium ion (referred to as The Phillips Mechanism).

<applet load='aln_1H6M_to_1HEW_2.pdb' size='200' frame='true' align='left' caption='NAG-2-deoxy-2-fluoro-glucosyl fluoride (NAG2FGlcF) bound to Glu35Gln HEW Lysozyme PDBid 1H6M' scene='User:Judy_Voet/Lysozyme/1h6m/3'/>

Then, in 2001, Stephen Withers published <scene name='User:Judy_Voet/Lysozyme/1h6m/3'>1H6M</scene>,<ref>PMID 11518970</ref> in which Glu 35 had been mutated to Gln to remove the general acid catalyst. The substrate contained NAG-2-fluoro-glucosyl fluoride (NAG2FGlcF). The fluoro group on C-1 does not require acid catalysis to be a good leaving group, and the remaining saccharide, in the absence of the acid necessary to catalyse the second step of the reaction, was demonstrated to form a <scene name='User:Judy_Voet/Lysozyme/Covalent/1'> covalent intermediate</scene>. In this <scene name='User:Judy_Voet/Lysozyme/Superposition/2'>superposition</scene> of the half chair model with 1HEW (greens) and the covalent intermediate in 1H6M (blues), note the relatively small motions of Asp 52 and C1 of the sugar ring in going from the model to the covalent intermediate. to observe the motion from the <scene name='User:Judy_Voet/Lysozyme/Asp52_halfchair/1'>half-chair</scene> to the <scene name='User:Judy_Voet/Lysozyme/Covalent/2'>covalent intermediate</scene> just toggle between the two green links.

== 3D Structures of Lysozyme ==

===Lys===

[[2x0a]], [[3iju]], [[3ijv]], [[3a8z]], [[2w1y]], [[2w1m]], [[2w1x]], [[2w1l]], [[3e3d]], [[3exd]], [[2zq3]], [[2zq4]], [[3b72]], [[3b6l]], [[2z12]], [[2z18]], [[2z19]], [[2vb1]], [[2hu3]], [[2hub]], [[2htx]], [[2hu1]], [[2yvb]], [[2epe]], [[2g4p]], [[2g4q]], [[2cgi]], [[2b5z]], [[2d4k]], [[2d91]], [[2f2n]], [[2fbb]], [[2c8o]], [[2c8p]], [[2a6u]], [[2aub]], [[2blx]], [[2bly]], [[2a7d]], [[2a7f]], [[1wtm]], [[1wtn]], [[1w6z]], [[1vdp]], [[1vdq]], [[1vds]], [[1vdt]], [[1ved]], [[1v7t]], [[1ps5]], [[2cds]], [[1lj3]], [[1lj4]], [[1lje]], [[1ljf]], [[1ljg]], [[1ljh]], [[1lji]], [[1ljj]], [[1ljk]], [[1jis]], [[1jit]], [[1jiy]], [[1jj0]], [[1jj1]], [[1jj3]], [[1iee]], [[1qio]], [[1f0w]], [[1f10]], [[1dpx]], [[1c10]], [[1qtk]], [[1lz8]], [[1lz9]], [[1bhz]], [[1bgi]], [[1bwh]], [[1bwi]], [[1bwj]], [[1bvx]], [[1hsw]], [[1hsx]], [[1lpi]], [[4lzt]], [[3lzt]], [[1aki]], [[1jpo]], [[1rfp]], [[193l]], [[194l]], [[5lym]], [[1lza]], [[3lyt]], [[4lyt]], [[5lyt]], [[6lyt]], [[2lzt]], [[1lzt]], [[1lzh]], [[2lzh]], [[7lyz]], [[1lyz]], [[2lyz]], [[3lyz]], [[4lyz]], [[5lyz]], [[6lyz]] - HEWL – chicken 
[[1xei]], [[1xej]], [[1xek]], [[1uco]], [[1lma]], [[4lym]] – HEWL low hydration 
[[1lsa]], [[1lsb]], [[1lsc]], [[1lsd]], [[1lse]], [[1lsf]], [[1lys]] – HEWL temperature influence 
[[2lym]], [[3lym]] – HEWL pressure influence 
[[132l]] – HEWL methylated 
[[1rcm]] – HEWL 3 S-S form 
[[2xbr]], [[2xbs]]- HEWL– Raman crystallography 
[[2zwb]], [[1io5]], [[1lzn]] - HEWL– Neutron 
[[1gxv]], [[1gxx]], [[1e8l]] - HEWL- NMR 
[[2hs7]], [[2hso]], [[2hs9]]- HEWL– Powder diffraction 
[[1ir7]], [[1ir8]], [[1ir9]], [[1ioq]], [[1ior]], [[1ios]], [[1iot]], [[1flq]], [[1flu]], [[1flw]], [[1fly]], [[1fn5]], [[1kxw]], [[1kxx]], [[1kxy]], [[1uia]], [[1uib]], [[1uic]], [[1uid]], [[1uie]], [[1uif]], [[1uig]], [[1uih]], [[1lsm]], [[1lsn]], [[1hel]], [[1hem]], [[1hen]], [[1heo]], [[1hep]], [[1heq]], [[1her]] – HEWL (mutant) 
[[1lyo]], [[2lyo]], [[3lyo]], [[4lyo]] – HEWL cross-linked 
[[1xft]] - tuLys – turkey - Powder diffraction 
[[1jse]], [[1tew]], [[135l]], [[2lz2]], [[1lz2]] – tuLys 
[[3lz2]] – tuLys - Laue 
[[3ab6]] – Lys + NAG3 – Hard clam 
[[2x8r]] – Lys GH25 – ''Aspergillus fumigatus'' 
[[3mgw]] – Lys G – Atlantic salmon 
[[3gxk]], [[3gxr]] – Lys G + NAG – Atlantic cod 
[[2fbd]] – HfLys 1 
[[3cb7]] – HfLys 2 
[[2zij]], [[2zik]], [[2zil]], [[2nwd]], [[1iwt]], [[1iwu]], [[1iwv]], [[1iww]], [[1iwx]], [[1iwy]], [[1iwz]], [[1jwr]], [[1jsf]], [[1rex]], [[1lz1]] – hLys – human 
[[1w08]], [[1ix0]], [[1ioc]], [[1ip1]], [[1ip2]], [[1ip3]], [[1ip4]], [[1ip5]], [[1ip6]], [[1ip7]], [[1qsw]], [[1gev]], [[1gez]], [[1gf0]], [[1gf3]], [[1gf4]], [[1gf5]], [[1gf6]], [[1gf7]], [[1i1z]], [[1i20]], [[1i22]], [[1gfr]], [[1gft]], [[1gfu]], [[1gfv]], [[1gf8]], [[1gf9]], [[1gfa]], [[1gfe]], [[1gfg]], [[1gfh]], [[1gfj]], [[1gfk]], [[1inu]], [[1gdx]], [[1ge0]], [[1ge1]], [[1ge2]], [[1ge3]], [[1ge4]], [[1gdw]], [[1gaz]], [[1gb0]], [[1gb2]], [[1gb3]], [[1gb5]], [[1gb6]], [[1gb7]], [[1gb8]], [[1gb9]], [[1gbo]], [[1gbw]], [[1gbx]], [[1gby]], [[1gbz]], [[1gay]], [[1eq4]], [[1eq5]], [[1eqe]], [[1c7p]], [[1di3]], [[1di4]], [[1di5]], [[1c43]], [[1c45]], [[1c46]], [[1ckg]], [[1cj6]], [[1cj7]], [[1cj8]], [[1cj9]], [[1ckc]], [[1ckd]], [[1ckf]], [[1ckh]], [[1b5z]], [[1b70]], [[1b7q]], [[1b7r]], [[1b7s]], [[1b7l]], [[1b7m]], [[1b7n]], [[1b7p]], [[1b5u]], [[1b5v]], [[1b5w]], [[1b5x]], [[1b5y]], [[1bb3]], [[1bb4]], [[2bqa]], [[2bqb]], [[2bqc]], [[2bqd]], [[2bqe]], [[2bqf]], [[2bqg]], [[2bqh]], [[2bqi]], [[2bqj]], [[2bqk]], [[2bql]], [[2bqm]], [[2bqn]], [[2bqo]], [[2mea]], [[2meb]], [[2mec]], [[2med]], [[2mee]], [[2mef]], [[2meg]], [[2meh]], [[2mei]], [[1wqm]], [[1wqn]], [[1wqo]], [[1wqp]], [[1wqq]], [[1wqr]], [[2heb]], [[2hea]], [[2hec]], [[2hed]], [[2hee]], [[2hef]], [[1jka]], [[1jkb]], [[1jkc]], [[1jkd]], [[1loz]], [[1lyy]], [[1oua]], [[1oub]], [[1ouc]], [[1oud]], [[1oue]], [[1ouf]], [[1oug]], [[1ouh]], [[1oui]], [[1ouj]], [[207l]], [[208l ]], [[1yam]], [[1yan]], [[1yao]], [[1yap]], [[1yaq]], [[1lmt]], [[1lhh]], [[1lhi]], [[1lhj]], [[1lhk]], [[1lhl]], [[133l]], [[134l]], [[1lz4]], [[1lz5]], [[1lz6]], [[1laa]], [[1tay]], [[1tby]], [[1tcy]], [[1tdy]], [[2lhm]], [[3lhm]] – hLys (mutant) 
[[1iy3]], [[1iy4]] – hLys - NMR 
[[2z2f]] – Lys – Bovine 
[[2cwi]], [[1el1]], [[1qqy]] – dLys - dog 
[[2z2e]] – dLys (mutant) 
[[1i56]] – dLys – NMR 
[[2dqa]] – Lys – ''Tapes japonica'' 
[[2gv0]] – Lys – Soft-shelled turtle 
[[1ivm]] – mLys M – NMR – mouse 
[[1jfx]] – Lys – ''Streptomyces coelicolor'' 
[[1gd6]] – Lys – ''Bombyx mori'' 
[[1jug]] – Lys – Echidna 
[[1dkj]] – BqLys – Bobwhite quail 
[[2ihl]] – Lys – Japanese quail 
[[1gbs]] – BsLys – Black swan 
[[1lmn]] – RtLys – Rainbow trout 
[[2eql]] – Lys – horse 
[[1ghl]] – phLys – pheasant 
[[1hhl]] – GfLys – Guinea fowl 
[[1lhm]] – Lys (mutant) – yeast 

===Lys small molecules complexes===

[[3fe0]], [[2d4i]], [[2d4j]], [[1v7s]] - HEWL+ D2O 
[[3m3u]] – HEWL Trp fluorescence 
[[2xjw]] - HEWL + CO 
[[1hf4]], [[1lks]] – HEWL + NO3 
[[3a34]], [[3ems]] - HEWL + arginine 
[[2xth]] – cLys + inhibitor K2PtBr6 
[[3a90]], [[3a91]], [[3a92]], [[3a93]], [[3a94]], [[3a95]], [[3a96]], [[3kam]], [[2pc2]], [[2bpu]], [[1t3p]], [[1h87]] – HEWL + rare earth 
[[2d6b]], [[2hg0]], [[1vat]], [[1gwd]], [[1b2k]], [[1lkr]], [[1azf]], [[8lyz]]- HEWL+ halogen 
[[1vat]] - HEWL + Xe 
[[1n4f]] - HEWL + As 
[[2i6z]] - HEWL + Pt drug 
[[2zyp]] - HEWL + poly (allyl amine) 
[[2f30]], [[2f4a]] – HEWL + urea derivative 
[[2f4g]], [[1ykx]], [[1yky]], [[1ykz]], [[1yl0]], [[1yl1]], [[1z55]] - HEWL + alcohol 
[[1dpw]] – HEWL + MPD 
[[1lcn]] – HEWL + SCN 
[[2zxs]] - HEWL with glycine-amide 
[[2h9j]], [[2h9k]], [[1yik]], [[1yil]] - HEWL + cyclam derivative 
[[1b0d]] – HEWL + p-toluene-sulfonate 
[[2q0m]] - HEWL + tricarbonylmanganese 
[[2war]] – HEWL (mutant) + chitopentaose 
[[2h5z]] – HfLys 1 + chitotetraose – House fly 
[[1hnl]] – hLys + glutathione 
[[1dkk]] – BqLys + NO3 

===Lys complex with glucoside===

[[3a3q]] – HEWL (mutant) + NAG 
[[1sf4]], [[1sf6]], [[1sf7]], [[1sfb]], [[1sfg]], [[1ja2]], [[1ja4]], [[1ja6]], [[1ja7]] – HEWL + NAG oligosaccharide – Powder diffraction 
[[1ubz]], [[1d6p]], [[1d6q]], [[1bb5]] – hLys (mutant) + glycoside 
[[1uc0]], [[1re2]], [[1rem]], [[1rey]], [[1rez]], [[1lzr]], [[1lzs]] - hLys + glycoside 
[[1ljn]], [[1jef]], [[1lzy]] – tuLys + glycoside 
[[1h6m]], [[1at5]], [[1at6]], [[1lzb]], [[1lzc]], [[1lzd]], [[1lze]], [[1lzg]], [[1hew ]]– HEWL + glycoside 
[[1lsy]], [[1lsz]] - HEWL (mutant) + glycoside 
[[1bb6]], [[1bb7]] – RtLys + glycoside 
[[1lmc]] – RtLys + bulgecin 
[[1lmo]], [[1lmp]], [[1lmq]] – RtLys + glucoside 
[[1lsp]] – BsLys + bulgecin 
[[153l]], [[154l]] – Lys +glucoside – goose 

===Phage Lys===

[[2oe4]], [[2oe7]], [[2oe9]], [[2oea]], [[1swz]], [[1cx6]], [[1qtc]], [[1qtd]], [[1qth]], [[1qsb]], [[1qs5]], [[1qs9]], [[1qtb]], [[256l]], [[206l]], [[167l]], [[168l]], [[169l]], [[170l]], [[171l]], [[172l]], [[173l]], [[174l]], [[175l]], [[176l]], [[177l]], [[178l]], [[181l]], [[182l]], [[183l]], [[184l]], [[185l]], [[186l]], [[187l]], [[188l]], [[1nhb]], [[137l]], [[216l]], [[152l]], [[149l]], [[150l]], [[151l]], [[1lyd]], [[2lzm]] - T4Lys – Enterobacteria phage T4 
[[138l]] – T4Lys cross-linked 
[[4lzm]], [[5lzm]], [[6lzm]], [[7lzm]] – T4Lys ionic strength 
[[3l2x]], [[3k2r]], [[3g3v]], [[3g3w]], [[3g3x]], [[2q9d]], [[2q9e]], [[2igc]], [[2ntg]], [[2nth]], [[2ou8]], [[2ou9]], [[1zur]], [[1zwn]], [[1zyt]], [[2cuu]], [[2a4t]] – T4Lys (mutant) spin labeled 
[[3l64]], [[3hwl]], [[3jr6]], [[3gui]], [[3c7w]], [[3c7y]], [[3c7z]], [[3c80]], [[3c81]], [[3c82]], [[3c83]], [[3c8q]], [[3c8r]], [[3c8s]], [[3cdo]], [[3cdq]], [[3cdr]], [[3cdt]], [[3cdv]], [[3f8v]], [[3f9l]], [[3fa0]], [[3fad]], [[3fi5]], [[3dke]], [[3dmv]], [[2o4w]], [[2o79]], [[2o7a]], [[2huk]], [[2hul]], [[2hum]], [[2b7x]], [[2b6t]], [[2b6w]], [[2b6x]], [[2b6y]], [[2b6z]], [[2b70]], [[2b72]], [[2b73]], [[2b74]], [[2b75]], [[1sx7]], [[1swy]], [[1sx2]], [[1t6h]], [[1ssw]], [[1ssy]], [[1t8f]], [[1t8g]], [[1t8a]], [[1t97]], [[1p56]], [[1p5c]], [[1p2l]], [[1p2r]], [[1p36]], [[1p37]], [[1p3n]], [[1p46]], [[1p64]], [[1p6y]], [[1p7s]], [[1pqd]], [[1pqi]], [[1pqj]], [[1pqk]], [[1pqm]], [[1pqo]], [[1oyu]], [[1ks3]], [[1kw5]], [[1kw7]], [[1ky0]], [[1ky1]], [[1l0j]], [[1l0k]], [[1lw9]], [[1lwg]], [[1lwk]], [[1lpy]], [[1llh]], [[1lgu]], [[1li6]], [[1jtm]], [[1jtn]], [[1jqu]], [[1kni]], [[1g06]], [[1g07]], [[1g0g]], [[1g0j]], [[1g0k]], [[1g0l]], [[1g0m]], [[1g0p]], [[1g0q]], [[1g1v]], [[1g1w]], [[1i6s]], [[257l]], [[258l]], [[260l]], [[1epy]], [[1b6i]], [[1cu6]], [[1d9w]], [[1ctw]], [[1cu0]], [[1cu2]], [[1cu3]], [[1cu5]], [[1cv1]], [[1cv4]], [[1cv5]], [[1cv6]], [[1cvk]], [[1cx7]], [[1d2w]], [[1d2y]], [[1d3f]], [[1d3j]], [[1d3m]], [[1d3n]], [[1cv3]], [[1qt3]], [[1qt4]], [[1qt5]], [[1qt6]], [[1qt7]], [[1qt8]], [[1qtv]], [[1qtz]], [[1qud]], [[1qug]], [[1quh]], [[1quo]], [[1qsq]], [[261l]], [[262l]], [[259l]], [[220l]], [[222l]], [[223l]], [[225l]], [[226l]], [[227l]], [[228l]], [[229l]], [[235l]], [[236l]], [[237l]], [[238l]], [[239l]], [[240l]], [[241l]], [[242l]], [[243l]], [[244l]], [[245l]], [[246l]], [[247l]], [[248l]], [[249l]], [[250l]], [[251l]], [[252l]], [[253l]], [[254l]], [[255l]], [[230l]], [[231l]], [[232l]], [[233l]], [[234l]], [[209l]], [[210l]], [[211l]], [[212l]], [[213l]], [[214l]], [[215l]], [[218l]], [[219l]], [[180l]], [[195l]], [[196l]], [[197l]], [[198l]], [[199l]], [[200l]], [[190l]], [[191l]], [[192l]], [[189l]], [[155l]], [[156l]], [[157l]], [[158l]], [[159l]], [[160l]], [[161l]], [[162l]], [[163l]], [[164l]], [[165l]], [[166l]], [[129l]], [[130l]], [[131l]], [[140l]], [[141l]], [[142l]], [[143l]], [[144l]], [[145l]], [[146l]], [[147l]], [[201l]], [[205l]], [[221l]], [[224l]], [[102l]], [[103l]], [[104l]], [[107l]], [[108l]], [[109l]], [[110l]], [[111l]], [[112l]], [[113l]], [[114l]], [[115l]], [[118l]], [[119l]], [[120l]], [[122l]], [[123l]], [[125l]], [[126l]], [[127l]], [[128l]], [[1dya]], [[1dyb]], [[1dyc]], [[1dyd]], [[1dye]], [[1dyf]], [[1dyg]], [[1l00]], [[1l85]], [[1l86]], [[1l87]], [[1l88]], [[1l89]], [[1l90]], [[1l91]], [[1l92]], [[1l93]], [[1l94]], [[1l95]], [[1l96]], [[1l97]], [[1l98]], [[1l99]], [[1lye]], [[1lyf]], [[1lyg]], [[1lyh]], [[1lyi]], [[1lyj]], [[217l]], [[1tla]], [[1l77]], [[1l79]], [[1l80]], [[1l81]], [[1l82]], [[2l78]], [[1l36]], [[1l37]], [[1l38]], [[1l39]], [[1l40]], [[1l41]], [[1l42]], [[1l43]], [[1l44]], [[1l45]], [[1l46]], [[1l47]], [[1l48]], [[1l49]], [[1l50]], [[1l51]], [[1l52]], [[1l53]], [[1l54]], [[1l55]], [[1l56]], [[1l57]], [[1l58]], [[1l59]], [[1l60]], [[1l61]], [[1l62]], [[1l63]], [[1l64]], [[1l65]], [[1l66]], [[1l67]], [[1l68]], [[1l69]], [[1l70]], [[1l71]], [[1l72]], [[1l73]], [[1l74]], [[1l75]], [[1l76]], [[1l17]], [[1l18]], [[1l19]], [[1l20]], [[1l21]], [[1l22]], [[1l23]], [[1l24]], [[1l25]], [[1l26]], [[1l27]], [[1l28]], [[1l29]], [[1l30]], [[1l31]], [[1l32]], [[1l33]], [[1l34]], [[1l35]], [[3lzm]], [[1l01]], [[1l02]], [[1l03]], [[1l04]], [[1l05]], [[1l06]], [[1l07]], [[1l08]], [[1l09]], [[1l10]], [[1l11]], [[1l12]], [[1l13]], [[1l14]], [[1l15]], [[1l16]] – T4Lys (mutant) 
[[1c60]], [[1c61]], [[1c62]], [[1c63]], [[1c64]], [[1c65]], [[1c66]], [[1c67]], [[1c68]], [[1c69]], [[1c6a]], [[1c6b]], [[1c6c]], [[1c6d]], [[1c6e]], [[1c6f]], [[1c6g]], [[1c6h]], [[1c6i]], [[1c6j]], [[1c6k]], [[1c6l]], [[1c6m]], [[1c6n]], [[1c6p]], [[1c6q]], [[1c6t]] - T4Lys (mutant) + noble gas 
[[3ht6]], [[3ht7]], [[3ht8]], [[3ht9]], [[3htb]], [[3hu8]], [[3huq]], [[3guj]], [[3guk]], [[3gul]], [[3gum]], [[3gun]], [[3guo]], [[3gup]], [[3dmx]], [[3dmz]], [[3dn0]], [[3dn1]], [[3dn2]], [[3dn3]], [[3dn4]], [[3dn6]], [[3dn8]], [[3dna]], [[2rb1]], [[2ray]], [[2raz]], [[2rb0]], [[2rb2]], [[2rbn]], [[2rbo]], [[2rbq]], [[2rbr]], [[2rbs]], [[2oty]],[[2otz]], [[1owy]], [[1owz]], [[1ov5]], [[1ov7]], [[1ovh]], [[1ovj]], [[1ovk]], [[1lgw]], [[1lgx]], [[1li2]], [[1li3]], [[1l83]], [[1l84]] – T4Lys (mutant) + benzene derivative 
[[3htd]], [[3htf]], [[3htg]], [[3hu9]], [[3hua]], [[3huk]], [[3hh3]], [[3hh4]], [[3hh5]], [[3hh6]], [[2rbp]], [[2ou0]], [[2f2q]], [[2f32]], [[2f47]], [[1xep]] – T4Lys (mutant) + inhibitor 
[[148l]] - T4Lys (mutant) + glucoside 
[[3d3d]], [[1d9u]] – lamLys + chitohexasaccharide 
[[1am7]] – lamLys - Enterobacteria phage λ 
[[2anv]], [[2anx]] – Lys (mutant)]] - Enterobacteria phage p22 
[[1xjt]], [[1xju]] - Lys - Enterobacteria phage p1 
[[1lba]] - T7Lys - Enterobacteria phage T7 

===Lys protein complex===

[[3m18]], [[3g3a]], [[3g3b]] - HEWL + Variable lymphocyte receptor – Marine lamprey 
[[3a67]], [[3a6b]], [[3a6c]], [[2yss]], [[2eiz]], [[2dqc]], [[2dqd]], [[2dqe]], [[2dqf]], [[2dqg]], [[2dqh]], [[2dqi]], [[2dqj]], [[1j1o]], [[1j1p]], [[1j1x]], [[1ic4]], [[1ic5]], [[1ic7]] – HEWL + mLys antibody HYHEL-10 (mutant) 
[[1xgp]], [[1xgq]], [[1xgr]], [[1xgt]], [[1xgu]] – HEWL + mLys antibody HYHEL-63 
[[3d9a]], [[2eks]], [[1ua6]], [[1c08]], [[3hfm]] – HEWL + mLys antibody HYHEL-10 
[[1uac]] - tuLys C + mLys antibody HYHEL-10 
[[1yqv]], [[2iff]] – HEWL + mLys antibody HYHEL-5 
[[1bql]] – BqLys + mLys antibody HYHEL-5 
[[1ndg]] – HEWL + mLys antibody HYHEL-8 
[[1ndm]] – HEWL + mLys antibody HYHEL-26 
[[1dqj]] - HEWL + mLys antibody HYHEL-63 
[[1nby]], [[1nbz]] – HEWL (mutant) + mLys antibody HYHEL-63 
[[1g7h]], [[1g7i]], [[1g7j]], [[1g7l]], [[1g7m]], [[1kip]], [[1kiq]], [[1kir]] – HEWL + mAnti-HEWL monoclonal antibody (mutant) 
[[1mlc]], [[1vfb]] - HEWL + mIGG1-κ D44.1 FAB 
[[1a2y]] - HEWL (mutant) + mIGG1-κ D1.3 FV 
[[1fdl]] - HEWL + mIGG1-κ D1.3 FAB 
[[1jhl]] – phLys + mIGG1-κ D11.15 FV 
[[1fbi]] – GfLys + mIGG1 F9.13.7 FAB 
[[2znw]], [[2znx]] – HEWL + hSCFV10 antibody 
[[1bvk]] - HEWL + hAnti Lys FV antibody 
[[1dzb]] – tuLys + mSCFV 1F9 
[[1zv5]], [[1zvh]], [[1zvy]], [[1zmy]], [[1ri8]], [[1rjc]], [[1xfp]], [[1jtp]], [[1jtt]], [[1jto]], [[1mel]] - HEWL + cAntibody heavy chain domain – camel 
[[1op9]] - hLys C + cAntibody heavy chain domain 
[[3otp]] – HEWL + EcProtease DO – ''Escherichia coli'' 
[[3f6z]] - HEWL + MLIC – ''Pseudomonas aeruginosa'' 
[[3eba]] – hLys C + hCABHUL6 
[[2qb0]], [[2qar]] – T4Lys/E80 TELSAM domain 
[[2i25]], [[2i26]] - HEWL +NsAntigen receptor PBLA8 variable domain – Nurse shark 
[[1sq2]], [[1t6v]] – HEWL +NsNew Antigen receptor variable domain 
[[1gpq]] – HEWL + EcInhibitor of Vertebrate Lys 
[[1aro]] – T7Lys + T7 RNA polymerase 

===Some Useful External Links===
[http://en.wikipedia.org/wiki/Lysozyme Lysozyme]

[http://en.wikipedia.org/wiki/Glycoside_hydrolase#Retaining_glycoside_hydrolases Retaining Glycoside Hydrolases]

===References===
<references/>

Hen Egg-White (HEW) Lysozyme

2011-04-20T18:08:56Z

Anne Goodling:

'''Introduction'''

Lysozyme - also known as muramidase, or glycoside hydrolase - is a powerful enzyme of biological significance found in abundance in tears, saliva, and human milk. In humans, it is encoded in the ''LYZ'' gene. Although it is responsible for the initial digestion of starches in the mouth, it is most widely identified as a non-specific defense in gram positive bacteria and in many species of fungi. Due to its antibacterial effects, it is a strong component of the innate immune system, and is an important part of an infant's diet to ward off diarrheal diseases. Since it is a small, easily available, and highly stable protein containing only 129 amino acid residues, it has been subject to extensive research regarding its function and structure. Hen Egg White (HEW) Lysozyme is shown below.

===History===

Lysozyme is an enzyme known for its unique ability to degrade the polysaccharide architecture of many kinds of cell walls, normally for the purpose of protection against bacterial infection<ref>Lysozyme. 2010. Citizendium.org. http://en.citizendium.org/wiki/Lysozyme</ref>. Its effects were first noticed by Laschtschenko in 1909. It was officially characterized and termed “lysozyme” by Alexander Fleming, the same person credited for the accidental discovery of penicillin.
The characterization of lysozyme in 1922 by Alexander Fleming was providential in that the undertaken experiment related to the discovery of lysozyme was not geared toward any knowledge of such a protein as lysozyme <ref>Lysozyme. 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>. During the unrelated experiment, nasal drippings were inadvertently introduced to a petri dish containing a bacterial culture, which culture consequently exhibited the results of an as yet unknown enzymatic reaction. The observation of this unknown reaction led to further research on the components of this reaction as well as to the corresponding identification of the newfound "lysozyme." Fleming's discovery was complemented by David C. Phillips' 1965 description of the three-dimensional structure of lysozyme via a 200 pm resolution model obtained from X-ray crystallography <ref>Lysozyme, 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>. Phillips' work was especially groundbreaking since Phillips had managed to successfully elucidate the structure of an enzyme via X-ray crystallography - a feat that had never before been accomplished<ref>Bugg, T. 1997. An Introduction to Enzyme and Coenzyme Chemistry. Blackwell Science Ltd., Oxford </ref>. Phillips' research also led to the first sufficiently described enzymatic mechanism of catalytic action <ref>1967. Proc R Soc Lond B Bio 167 (1009): 389–401.</ref>. Thus, Phillips' elucidation of the function of lysozyme led Phillips to reach a more general conclusion on the diversity of enzymatic chemical action in relation to enzymatic structure. Clearly, the findings of Phillips as well as the more general historical development of the understanding of the structure and function of lysozyme have been paramount to the more general realm of enzyme chemistry.

[[Image:nag-nam2.jpg|thumb|left|350px|Lysozyme Cleavage Site]]
<ref>Image from: http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/proteins/lysozyme.htm</ref>

'''Function'''

Lysozyme is known for damaging bacterial cell walls by catalyzing the hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid (NAM) and N-acetyl-D-glucosamine (NAG) residues in peptidoglycan, and between N-acetyl-D-glucosamine residues in chitodextrins. In this way, lysozyme is efficient in lysing the cell walls of both bacteria and fungi. The location of cleavage for lysozyme on this architectural theme is the β(1-4) glycosidic linkage connecting the C1 carbon of NAM to the C4 carbon of NAG.

The particular substrate of preference for this cleavage type is a (NAG-NAM)₃ hexasaccharide, within which substrate occurs the
cleaving target glycosidic bond, NAM₄-β-O-NAG₅. The individual hexasaccharide binding units are designated A-F, with NAM₄-β-O-NAG₅ glycosidic bond cleavage preference corresponding to a D-E unit glycosidic bond cleavage preference.

= Enzymatic Activity of Lysozyme =

Enzymes are designed to attract and to bind specific substrates. The active site of and lysozyme and its specific ligands are described in the following sections

==Mechanistic Features==

'''Zymogen of Lysozyme: Enzymatic Precursor'''

Zymogens are inactive enzyme precursors. Enzymes are developed in an inactive way to prevent the enzyme from digesting the cell that produced it. This process also prevents the enzyme from becoming active in the wrong portion of the body. Lysozyme's zymogen, simply titled “pre-lysozyme,” was sequenced in 1977 by R D Palmiter, J Gagnon, L H Ericsson and K A Walsh, and has since been sequenced much more extensively.

[[Image:jrip.jpg|thumb|left|350px|Mechanism of Lysozyme]]
<ref>Image from: http://www.google.com/imgres?imgurl=http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/pics-and-strucs/lysozyme-mech.gif&imgrefurl=http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/proteins/lysozyme.htm&usg=__ormapG4XKg-tR5GrMSOdSMTV4vE=&h=603&w=801&sz=7&hl=en&start=17&zoom=1&tbnid=nvr9gvFrUILDkM:&tbnh=143&tbnw=189&prev=/images%3Fq%3DThe%2Blysozyme%2Breaction%2Bmechanism%26um%3D1%26hl%3Den%26sa%3DN%26biw%3D1280%26bih%3D647%26tbs%3Disch:10%2C304&um=1&itbs=1&iact=hc&vpx=521&vpy=349&dur=448&hovh=191&hovw=254&tx=140&ty=48&ei=JQ_LTPKzLIjCsAPkzt2KDg&oei=IA_LTP74OsG78gapm-GFAQ&esq=2&page=2&ndsp=18&ved=1t:429,r:2,s:17&biw=1280&bih=647</ref>

'''Mechanism'''

The lysozyme mechanism of action results in the hydrolysis of a glycoside (hence the familial distinction of lysozyme as a glycosylase<ref>Lysozyme, 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>), which corresponds to the conversion of an acetal to a hemiacetal, which reaction (general degradation of glycosidic bond to units "capped" by newly formed hydroxyl groups) necessitates acid catalysis, since the conversion of acetal to hemiacetal involves the protonation of the reactant oxygen prior to actual bond cleavage. <ref>Pratt, C.W., Voet, D., Voet, J.G. Fundamentals of Biochemistry - Life at the Molecular Level - Third Edition. Voet, Voet and Pratt, 2008.</ref>. Furthermore, the transition state obtained from this protonation is a covalent, oxonium ion, intermediate that must obtain resonance stabilization. The need for some means of acid catalysis and covalent resonance stabilization is adequately provided by the Glu 35 and Asp 52 residues of lysozyme, respectively. The reaction mechanism of lysozyme is demonstrated below. In the following image, the reaction begins at the upper left-hand side, and proceeds according to reaction arrows.

As seen to the left, lysozyme works by hydrolyzing the glycosidic bond, distorting the bond between the NAM and NAG. This produces a glycosyl enzyme intermediate, which reacts with a water molecule to produce the product and the unchanged enzyme.

'''Active Site'''

The <scene name='Hen_Egg-White_(HEW)_Lysozyme/Act_site/2'>active site</scene> of lysozyme is formulated as a prominent cleft outlined by the two aforementioned catalytic amino acids, Glu 35 and Asp 52. The active site is geometrically bent to augment ligand binding, and the two amino acids interact with the ligand in the binding site. Asp52 is depicted in red, and Glu35 is depicted in green.

<applet load='1hew' size='350' frame='true' align='right' caption='' />

==Binding==
'''Ligands'''

A ligand is able to bind to the active site of an enzyme to form a biologically relevant complex. The model to the right shows a space-filling model of lysozyme with the protein distinguishable in brown and the ligand distinguishable in green. Another model of the ligand can be seen in this
<scene name='Hen_Egg-White_(HEW)_Lysozyme/Ligand/1'>ribbon diagram</scene> <scene name='Sandbox_39/Ribbon_ligand/1'>ribbon diagram</scene>, with the ligand protruding as a space-filling model from the active site. Here, it is clear that the ligand is a polysaccharide.

The lysozyme reaction is characterized by hydrolysis of the beta (1-4) glycosidic bond between NAM and NAG. Lysozyme has a very specific active site, which can bind only six sugar rings from a polysaccharide chain. Once lysozyme binds to this chain, it hydrolyzes them. These six sugar rings represent the ligand of lysozyme. The lysozyme then distorts the fourth sugar in the six-membered complex, producing stress on the molecule and breaking the glycosidic bond.

The amino acid side-chains Glu35 and Asp52 are critical to the activity of this enzyme. Glu35 acts as a proton donor to the glycosidic bond, cleaving the C-O bond in the substrate, and Asp52 acts as a nucleophile to generate a glycosyl enzyme intermediate. The glycosyl enzyme intermediate then reacts with a water molecule to give the product of hydrolysis.

'''Inhibitors'''

Lysozyme is best inhibited by small saccharides which act competitively with the natural substrate. The smaller saccharides will bind to the first three binding sites of the cleft (sites A-C), but will not reach sites D and E, where the enzyme cuts the glycosidic bond. So, the competitive inhibitor will stick in the cleft, not allowing the substrate to bind to the enzyme complex.<ref>http://mcdb-webarchive.mcdb.ucsb.edu/sears/biochemistry/tw-enz/lysozyme/HEWL/lysozyme-overview.htm</ref> Several known inhibitors of lysozyme are: SDS, N-acetyl-D-glucosamine, and various alcohols and oxidizing agents.<ref>http://www.worthington-biochem.com/ly/default.html</ref>

<applet load='1hew' size='350' frame='true' align='left' caption='' />

= Composition and Structure of Lysozyme =

All proteins consist of carbon, hydrogen, nitrogen, oxygen, and sulfur, as do most organic molecules. Enzymes are composed in such a way as to maximize their reactivity with their desired substrate, increasing the efficiency of biological reactions. The <scene name='Sandbox_39/Elements/1'>composition of lysozyme</scene> can be seen on the left, with the carbon atoms outlined in gray, oxygen atoms in red, nitrogen atoms in blue, sulfur atoms in yellow, and the three-letter abbreviation for the <scene name='Sandbox_39/Amino_acid_residues/1'>amino acid residues</scene> in purple.

Lysozyme, like all proteins, also contains a <scene name='Sandbox_39/C_and_n_terminal_residues/1'> 3'C and 5'N terminal </scene>, and these can be seen by following the colors of the rainbow across the molecule. Starting at the red end, the 3' C terminal end, one can work the entire way through to the 5' N terminal end, showing the folding pattern and chain of the protein.

== Secondary Structure ==

Lysozyme contains five <scene name='Sandbox_38/A/2'>alpha helical</scene> regions and five regions containing <scene name='Sandbox_38/B/1'>beta sheets</scene> as displayed in this <scene name='Sandbox_38/Alphab/1'>image</scene>. Linking these secondary structures, a number of beta turns and a large number of random coils make up the remainder of the polypeptide backbone. The polypeptide backbone of lysozyme involved in the 3 antiparallel beta sheets display the beta hairpin motif of supersecondary structure. This depiction of lysozyme contains an antiparallel beta-pleated sheet, which contributes greatly to the stability of the molecule by providing the correct alignment of hydrogen bonds. Lysozyme also contains a great deal of random coil, which is seen in the white regions of the molecule.

==Amino Acid Residues==

The amino acids present in the lysozyme polypeptide sequence have a direct influence not only on primary structure, but also on the secondary and tertiary structures, which can be influenced by polarity and charge of the sidechains. The various amino acid <scene name='Sandbox_38/Aminoi/1'>residues</scene> differ in their properties because of the great variety of side chains present on each amino acid. Polar and nonpolar (and charged and uncharged) side chains lead to various degrees of hydrophobicity and hydrophilicity, which affects protein folding. In lysozyme, these <scene name='Sandbox_38/Sc/1'>side chains</scene> are displayed for each amino acid residue.

= Bonding Interactions =

'''Disulfide Bonding in Lysozyme'''

Lysozyme contains four <scene name='Sandbox_39/Disulfide_bonds/1'>disulfide bonds</scene> involving eight cysteine residues, which are highlighted in yellow on the left. Disulfide bonds are intramolecular forces that stabilize the tertiary structure of many proteins. Disulfide bonds are present in four locations in lysozyme: between Cys 6 and Cys 127, between Cys 30 and Cys 115, between Cys 64 and Cys 80 and between Cys 76 and Cys 94.

'''Hydrogen Bonding'''

In all proteins <scene name='Sandbox_39/Hydrogen_bonds/2'>hydrogen bonds</scene> are essential for stability. In this ribbon diagram, the hydrogen bonds can be seen between the secondary structures of lysozyme highlighted in orange. Since the double bonds of the alpha carbons in the main chain of lysozyme cause torsional strain, lysozyme is limited to very specific hydrogen bonding between the amino acid residues. This representation clearly shows how crucial hydrogen bonding is to help maintain the stability of the protein.

<applet load='1hew' size='350' frame='true' align='left' caption='' />

= Intermolecular Interactions =

'''Hydrophobicity'''

Lysozyme contains both hydrophobic and hydrophilic regions ( <scene name='Sandbox_39/Hydrophobicity/2'>Hydrophobicity</scene> ). The hydrophilic effect, or the desire for proteins to be at a specific position regarding water, is the single most important determinant of protein folding. These regions can be displayed with the hydrophobic regions in gray and the polar, hydrophillic regions in purple. This coloration highlights the location of these regions, showing that the majority of the hydrophobic regions are inside of the protein and that the majority of the hydrophillic regions are on the outside of the protein.

'''Polarity'''

The nature of the amino acid sidechains in the lysozyme polypeptide sequence leads to regions of varying hydrophobicities and polarities of the enzyme structure. The presence of certain regions of hydrophilicity and hydrophobicity is a driving force in determining protein structure when folding. The varying polarities of the side chains influence the locations of residues in the enzyme structure. Nonpolar residues appear blue, and polar residues appear red in the following <scene name='Sandbox_38/Non_polar_blue/1'>polarity</scene> display of lysozyme. Nonpolar residues will display hydrophobic tendencies occurring mostly on the interior of the enzyme while polar residues will increase in abundance on the surface of the protein in order to increase contact with the aqueous solvent so as to satisfy their hydrophilic nature. By observing a space-filled structural depiction of <scene name='Sandbox_38/Non_polar_blu/1'>lysozyme polarity</scene> with polar molecules colored red and nonpolar molecules colored blue the influence of polarity on nucleotide arrangement and protein folding is evident, with the blue (nonpolar) regions inside the red (polar) regions. The presence of <scene name='Sandbox_39/Water/1'>water</scene> interacting with the various hydrophilic residues is depicted to further display how polarity affects structure. Water is depicted as yellow, and the polar and nonpolar regions remain their respective color.

'''Charge'''

Charges of the various regions of the lysozyme structure display a hydrophilic nature and thus also affect the location of that region of polypeptides and the overall folding of the protein. Charged regions of the protein will display hydrophilic tendencies and therefore will most often be located on the surface of the lysozyme molecule where they can interact with the aqueous solvent. Non-charged portions will display hydrophobic tendencies and be located on the interior of the molecule. The effect of various <scene name='Sandbox_38/Rb/1'>charges</scene> on protein structure can be visualized with charged molecules represented by red anionic and blue cationic regions, and uncharged regions colored in grey. This depiction of lysozyme uses a spacefill representation of lysozyme to depict <scene name='Sandbox_38/Chargeddd/1'>charges</scene>.

= Applications of Lysozyme =

Since lysozyme has been widely recognized for its antibacterial and antifungal properties, it has a wide variety of uses both in biochemical and pharmaceutical applications. In molecular biology, lysozyme is often used in the alkaline-lysis procedure for extracting and isolating plasmid DNA. It is used extensively in the pharmaceutical field for destroying gram-positive bacteria, and can be used to support already-existing immune defenses to fight bacterial infections. This enzyme is particularly important for preventing bacterial diseases in infants. Because of its antibacterial properties, lysozyme can also be used in the food industry to help prevent spoilage of foods.

= Discovery and Applications of Hen Egg-White Lysozyme=

<applet load='aln_1H6M_to_1HEW_2.pdb' size='300' frame='true' align='right' caption=' Hen Egg White (HEW) Lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to the active site, PDBid 1HEW' scene='User:Judy_Voet/Lysozyme/Lysozyme1/16' />
Lysozyme was the first enzyme whose X-ray structure was determined <ref> PMID 5840126</ref><ref>Phillips, D. C. The hen egg white lysozyme molecule. Proc. Natl Acad. Sci. USA 57, 483-495 (1967)</ref>. This <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>scene </scene> shows Hen Egg White (HEW) lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to a cleft in the enzyme. David Phillips, who determined the structure in 1965, saw that the cleft was large enough to fit three more saccharide units.
He therefore built a model extending the trisaccharide to a
<scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> that fits into the cleft, labeling the sugar subsites A-F<ref> coordinates of the model kindly provided by Louise Johnson</ref>. Alternately click on <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>trisaccharide</scene> and <scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> to turn the modeled portion of the hexasaccharide on and off.

The interesting thing about the model was that the only way that the hexasaccharide would fit into the cleft was if the 4th saccharide (in subsite D) was strained into a <scene name='User:Judy_Voet/Lysozyme/Half-chair/2'>half-chair conformation</scene>. This conformation is what would be necessary for the formation of an oxocarbenium ion (oxionium ion). When the model was studied, <scene name='User:Judy_Voet/Lysozyme/Glu_35/1'>Glu 35</scene> was found to be in an ideal location to act as a general acid catalyst, 3.34 Angstroms from the bridging oxygen between the 4th and 5th saccharide units. <scene name='User:Judy_Voet/Lysozyme/Asp_52/2'>Asp 52</scene> appeared to be too far away (2.69 angstroms) in the static lysozyme structure to have formed a covalent bond with C1 of the half-chair model in the D site, and no covalent intermediate had ever been detected, so Phillips proposed that it acted as an electrostatic stabilizer of the oxonium ion (referred to as The Phillips Mechanism).

<applet load='aln_1H6M_to_1HEW_2.pdb' size='200' frame='true' align='left' caption='NAG-2-deoxy-2-fluoro-glucosyl fluoride (NAG2FGlcF) bound to Glu35Gln HEW Lysozyme PDBid 1H6M' scene='User:Judy_Voet/Lysozyme/1h6m/3'/>

Then, in 2001, Stephen Withers published <scene name='User:Judy_Voet/Lysozyme/1h6m/3'>1H6M</scene>,<ref>PMID 11518970</ref> in which Glu 35 had been mutated to Gln to remove the general acid catalyst. The substrate contained NAG-2-fluoro-glucosyl fluoride (NAG2FGlcF). The fluoro group on C-1 does not require acid catalysis to be a good leaving group, and the remaining saccharide, in the absence of the acid necessary to catalyse the second step of the reaction, was demonstrated to form a <scene name='User:Judy_Voet/Lysozyme/Covalent/1'> covalent intermediate</scene>. In this <scene name='User:Judy_Voet/Lysozyme/Superposition/2'>superposition</scene> of the half chair model with 1HEW (greens) and the covalent intermediate in 1H6M (blues), note the relatively small motions of Asp 52 and C1 of the sugar ring in going from the model to the covalent intermediate. to observe the motion from the <scene name='User:Judy_Voet/Lysozyme/Asp52_halfchair/1'>half-chair</scene> to the <scene name='User:Judy_Voet/Lysozyme/Covalent/2'>covalent intermediate</scene> just toggle between the two green links.

== 3D Structures of Lysozyme ==

===Lys===

[[2x0a]], [[3iju]], [[3ijv]], [[3a8z]], [[2w1y]], [[2w1m]], [[2w1x]], [[2w1l]], [[3e3d]], [[3exd]], [[2zq3]], [[2zq4]], [[3b72]], [[3b6l]], [[2z12]], [[2z18]], [[2z19]], [[2vb1]], [[2hu3]], [[2hub]], [[2htx]], [[2hu1]], [[2yvb]], [[2epe]], [[2g4p]], [[2g4q]], [[2cgi]], [[2b5z]], [[2d4k]], [[2d91]], [[2f2n]], [[2fbb]], [[2c8o]], [[2c8p]], [[2a6u]], [[2aub]], [[2blx]], [[2bly]], [[2a7d]], [[2a7f]], [[1wtm]], [[1wtn]], [[1w6z]], [[1vdp]], [[1vdq]], [[1vds]], [[1vdt]], [[1ved]], [[1v7t]], [[1ps5]], [[2cds]], [[1lj3]], [[1lj4]], [[1lje]], [[1ljf]], [[1ljg]], [[1ljh]], [[1lji]], [[1ljj]], [[1ljk]], [[1jis]], [[1jit]], [[1jiy]], [[1jj0]], [[1jj1]], [[1jj3]], [[1iee]], [[1qio]], [[1f0w]], [[1f10]], [[1dpx]], [[1c10]], [[1qtk]], [[1lz8]], [[1lz9]], [[1bhz]], [[1bgi]], [[1bwh]], [[1bwi]], [[1bwj]], [[1bvx]], [[1hsw]], [[1hsx]], [[1lpi]], [[4lzt]], [[3lzt]], [[1aki]], [[1jpo]], [[1rfp]], [[193l]], [[194l]], [[5lym]], [[1lza]], [[3lyt]], [[4lyt]], [[5lyt]], [[6lyt]], [[2lzt]], [[1lzt]], [[1lzh]], [[2lzh]], [[7lyz]], [[1lyz]], [[2lyz]], [[3lyz]], [[4lyz]], [[5lyz]], [[6lyz]] - HEWL – chicken 
[[1xei]], [[1xej]], [[1xek]], [[1uco]], [[1lma]], [[4lym]] – HEWL low hydration 
[[1lsa]], [[1lsb]], [[1lsc]], [[1lsd]], [[1lse]], [[1lsf]], [[1lys]] – HEWL temperature influence 
[[2lym]], [[3lym]] – HEWL pressure influence 
[[132l]] – HEWL methylated 
[[1rcm]] – HEWL 3 S-S form 
[[2xbr]], [[2xbs]]- HEWL– Raman crystallography 
[[2zwb]], [[1io5]], [[1lzn]] - HEWL– Neutron 
[[1gxv]], [[1gxx]], [[1e8l]] - HEWL- NMR 
[[2hs7]], [[2hso]], [[2hs9]]- HEWL– Powder diffraction 
[[1ir7]], [[1ir8]], [[1ir9]], [[1ioq]], [[1ior]], [[1ios]], [[1iot]], [[1flq]], [[1flu]], [[1flw]], [[1fly]], [[1fn5]], [[1kxw]], [[1kxx]], [[1kxy]], [[1uia]], [[1uib]], [[1uic]], [[1uid]], [[1uie]], [[1uif]], [[1uig]], [[1uih]], [[1lsm]], [[1lsn]], [[1hel]], [[1hem]], [[1hen]], [[1heo]], [[1hep]], [[1heq]], [[1her]] – HEWL (mutant) 
[[1lyo]], [[2lyo]], [[3lyo]], [[4lyo]] – HEWL cross-linked 
[[1xft]] - tuLys – turkey - Powder diffraction 
[[1jse]], [[1tew]], [[135l]], [[2lz2]], [[1lz2]] – tuLys 
[[3lz2]] – tuLys - Laue 
[[3ab6]] – Lys + NAG3 – Hard clam 
[[2x8r]] – Lys GH25 – ''Aspergillus fumigatus'' 
[[3mgw]] – Lys G – Atlantic salmon 
[[3gxk]], [[3gxr]] – Lys G + NAG – Atlantic cod 
[[2fbd]] – HfLys 1 
[[3cb7]] – HfLys 2 
[[2zij]], [[2zik]], [[2zil]], [[2nwd]], [[1iwt]], [[1iwu]], [[1iwv]], [[1iww]], [[1iwx]], [[1iwy]], [[1iwz]], [[1jwr]], [[1jsf]], [[1rex]], [[1lz1]] – hLys – human 
[[1w08]], [[1ix0]], [[1ioc]], [[1ip1]], [[1ip2]], [[1ip3]], [[1ip4]], [[1ip5]], [[1ip6]], [[1ip7]], [[1qsw]], [[1gev]], [[1gez]], [[1gf0]], [[1gf3]], [[1gf4]], [[1gf5]], [[1gf6]], [[1gf7]], [[1i1z]], [[1i20]], [[1i22]], [[1gfr]], [[1gft]], [[1gfu]], [[1gfv]], [[1gf8]], [[1gf9]], [[1gfa]], [[1gfe]], [[1gfg]], [[1gfh]], [[1gfj]], [[1gfk]], [[1inu]], [[1gdx]], [[1ge0]], [[1ge1]], [[1ge2]], [[1ge3]], [[1ge4]], [[1gdw]], [[1gaz]], [[1gb0]], [[1gb2]], [[1gb3]], [[1gb5]], [[1gb6]], [[1gb7]], [[1gb8]], [[1gb9]], [[1gbo]], [[1gbw]], [[1gbx]], [[1gby]], [[1gbz]], [[1gay]], [[1eq4]], [[1eq5]], [[1eqe]], [[1c7p]], [[1di3]], [[1di4]], [[1di5]], [[1c43]], [[1c45]], [[1c46]], [[1ckg]], [[1cj6]], [[1cj7]], [[1cj8]], [[1cj9]], [[1ckc]], [[1ckd]], [[1ckf]], [[1ckh]], [[1b5z]], [[1b70]], [[1b7q]], [[1b7r]], [[1b7s]], [[1b7l]], [[1b7m]], [[1b7n]], [[1b7p]], [[1b5u]], [[1b5v]], [[1b5w]], [[1b5x]], [[1b5y]], [[1bb3]], [[1bb4]], [[2bqa]], [[2bqb]], [[2bqc]], [[2bqd]], [[2bqe]], [[2bqf]], [[2bqg]], [[2bqh]], [[2bqi]], [[2bqj]], [[2bqk]], [[2bql]], [[2bqm]], [[2bqn]], [[2bqo]], [[2mea]], [[2meb]], [[2mec]], [[2med]], [[2mee]], [[2mef]], [[2meg]], [[2meh]], [[2mei]], [[1wqm]], [[1wqn]], [[1wqo]], [[1wqp]], [[1wqq]], [[1wqr]], [[2heb]], [[2hea]], [[2hec]], [[2hed]], [[2hee]], [[2hef]], [[1jka]], [[1jkb]], [[1jkc]], [[1jkd]], [[1loz]], [[1lyy]], [[1oua]], [[1oub]], [[1ouc]], [[1oud]], [[1oue]], [[1ouf]], [[1oug]], [[1ouh]], [[1oui]], [[1ouj]], [[207l]], [[208l ]], [[1yam]], [[1yan]], [[1yao]], [[1yap]], [[1yaq]], [[1lmt]], [[1lhh]], [[1lhi]], [[1lhj]], [[1lhk]], [[1lhl]], [[133l]], [[134l]], [[1lz4]], [[1lz5]], [[1lz6]], [[1laa]], [[1tay]], [[1tby]], [[1tcy]], [[1tdy]], [[2lhm]], [[3lhm]] – hLys (mutant) 
[[1iy3]], [[1iy4]] – hLys - NMR 
[[2z2f]] – Lys – Bovine 
[[2cwi]], [[1el1]], [[1qqy]] – dLys - dog 
[[2z2e]] – dLys (mutant) 
[[1i56]] – dLys – NMR 
[[2dqa]] – Lys – ''Tapes japonica'' 
[[2gv0]] – Lys – Soft-shelled turtle 
[[1ivm]] – mLys M – NMR – mouse 
[[1jfx]] – Lys – ''Streptomyces coelicolor'' 
[[1gd6]] – Lys – ''Bombyx mori'' 
[[1jug]] – Lys – Echidna 
[[1dkj]] – BqLys – Bobwhite quail 
[[2ihl]] – Lys – Japanese quail 
[[1gbs]] – BsLys – Black swan 
[[1lmn]] – RtLys – Rainbow trout 
[[2eql]] – Lys – horse 
[[1ghl]] – phLys – pheasant 
[[1hhl]] – GfLys – Guinea fowl 
[[1lhm]] – Lys (mutant) – yeast 

===Lys small molecules complexes===

[[3fe0]], [[2d4i]], [[2d4j]], [[1v7s]] - HEWL+ D2O 
[[3m3u]] – HEWL Trp fluorescence 
[[2xjw]] - HEWL + CO 
[[1hf4]], [[1lks]] – HEWL + NO3 
[[3a34]], [[3ems]] - HEWL + arginine 
[[2xth]] – cLys + inhibitor K2PtBr6 
[[3a90]], [[3a91]], [[3a92]], [[3a93]], [[3a94]], [[3a95]], [[3a96]], [[3kam]], [[2pc2]], [[2bpu]], [[1t3p]], [[1h87]] – HEWL + rare earth 
[[2d6b]], [[2hg0]], [[1vat]], [[1gwd]], [[1b2k]], [[1lkr]], [[1azf]], [[8lyz]]- HEWL+ halogen 
[[1vat]] - HEWL + Xe 
[[1n4f]] - HEWL + As 
[[2i6z]] - HEWL + Pt drug 
[[2zyp]] - HEWL + poly (allyl amine) 
[[2f30]], [[2f4a]] – HEWL + urea derivative 
[[2f4g]], [[1ykx]], [[1yky]], [[1ykz]], [[1yl0]], [[1yl1]], [[1z55]] - HEWL + alcohol 
[[1dpw]] – HEWL + MPD 
[[1lcn]] – HEWL + SCN 
[[2zxs]] - HEWL with glycine-amide 
[[2h9j]], [[2h9k]], [[1yik]], [[1yil]] - HEWL + cyclam derivative 
[[1b0d]] – HEWL + p-toluene-sulfonate 
[[2q0m]] - HEWL + tricarbonylmanganese 
[[2war]] – HEWL (mutant) + chitopentaose 
[[2h5z]] – HfLys 1 + chitotetraose – House fly 
[[1hnl]] – hLys + glutathione 
[[1dkk]] – BqLys + NO3 

===Lys complex with glucoside===

[[3a3q]] – HEWL (mutant) + NAG 
[[1sf4]], [[1sf6]], [[1sf7]], [[1sfb]], [[1sfg]], [[1ja2]], [[1ja4]], [[1ja6]], [[1ja7]] – HEWL + NAG oligosaccharide – Powder diffraction 
[[1ubz]], [[1d6p]], [[1d6q]], [[1bb5]] – hLys (mutant) + glycoside 
[[1uc0]], [[1re2]], [[1rem]], [[1rey]], [[1rez]], [[1lzr]], [[1lzs]] - hLys + glycoside 
[[1ljn]], [[1jef]], [[1lzy]] – tuLys + glycoside 
[[1h6m]], [[1at5]], [[1at6]], [[1lzb]], [[1lzc]], [[1lzd]], [[1lze]], [[1lzg]], [[1hew ]]– HEWL + glycoside 
[[1lsy]], [[1lsz]] - HEWL (mutant) + glycoside 
[[1bb6]], [[1bb7]] – RtLys + glycoside 
[[1lmc]] – RtLys + bulgecin 
[[1lmo]], [[1lmp]], [[1lmq]] – RtLys + glucoside 
[[1lsp]] – BsLys + bulgecin 
[[153l]], [[154l]] – Lys +glucoside – goose 

===Phage Lys===

[[2oe4]], [[2oe7]], [[2oe9]], [[2oea]], [[1swz]], [[1cx6]], [[1qtc]], [[1qtd]], [[1qth]], [[1qsb]], [[1qs5]], [[1qs9]], [[1qtb]], [[256l]], [[206l]], [[167l]], [[168l]], [[169l]], [[170l]], [[171l]], [[172l]], [[173l]], [[174l]], [[175l]], [[176l]], [[177l]], [[178l]], [[181l]], [[182l]], [[183l]], [[184l]], [[185l]], [[186l]], [[187l]], [[188l]], [[1nhb]], [[137l]], [[216l]], [[152l]], [[149l]], [[150l]], [[151l]], [[1lyd]], [[2lzm]] - T4Lys – Enterobacteria phage T4 
[[138l]] – T4Lys cross-linked 
[[4lzm]], [[5lzm]], [[6lzm]], [[7lzm]] – T4Lys ionic strength 
[[3l2x]], [[3k2r]], [[3g3v]], [[3g3w]], [[3g3x]], [[2q9d]], [[2q9e]], [[2igc]], [[2ntg]], [[2nth]], [[2ou8]], [[2ou9]], [[1zur]], [[1zwn]], [[1zyt]], [[2cuu]], [[2a4t]] – T4Lys (mutant) spin labeled 
[[3l64]], [[3hwl]], [[3jr6]], [[3gui]], [[3c7w]], [[3c7y]], [[3c7z]], [[3c80]], [[3c81]], [[3c82]], [[3c83]], [[3c8q]], [[3c8r]], [[3c8s]], [[3cdo]], [[3cdq]], [[3cdr]], [[3cdt]], [[3cdv]], [[3f8v]], [[3f9l]], [[3fa0]], [[3fad]], [[3fi5]], [[3dke]], [[3dmv]], [[2o4w]], [[2o79]], [[2o7a]], [[2huk]], [[2hul]], [[2hum]], [[2b7x]], [[2b6t]], [[2b6w]], [[2b6x]], [[2b6y]], [[2b6z]], [[2b70]], [[2b72]], [[2b73]], [[2b74]], [[2b75]], [[1sx7]], [[1swy]], [[1sx2]], [[1t6h]], [[1ssw]], [[1ssy]], [[1t8f]], [[1t8g]], [[1t8a]], [[1t97]], [[1p56]], [[1p5c]], [[1p2l]], [[1p2r]], [[1p36]], [[1p37]], [[1p3n]], [[1p46]], [[1p64]], [[1p6y]], [[1p7s]], [[1pqd]], [[1pqi]], [[1pqj]], [[1pqk]], [[1pqm]], [[1pqo]], [[1oyu]], [[1ks3]], [[1kw5]], [[1kw7]], [[1ky0]], [[1ky1]], [[1l0j]], [[1l0k]], [[1lw9]], [[1lwg]], [[1lwk]], [[1lpy]], [[1llh]], [[1lgu]], [[1li6]], [[1jtm]], [[1jtn]], [[1jqu]], [[1kni]], [[1g06]], [[1g07]], [[1g0g]], [[1g0j]], [[1g0k]], [[1g0l]], [[1g0m]], [[1g0p]], [[1g0q]], [[1g1v]], [[1g1w]], [[1i6s]], [[257l]], [[258l]], [[260l]], [[1epy]], [[1b6i]], [[1cu6]], [[1d9w]], [[1ctw]], [[1cu0]], [[1cu2]], [[1cu3]], [[1cu5]], [[1cv1]], [[1cv4]], [[1cv5]], [[1cv6]], [[1cvk]], [[1cx7]], [[1d2w]], [[1d2y]], [[1d3f]], [[1d3j]], [[1d3m]], [[1d3n]], [[1cv3]], [[1qt3]], [[1qt4]], [[1qt5]], [[1qt6]], [[1qt7]], [[1qt8]], [[1qtv]], [[1qtz]], [[1qud]], [[1qug]], [[1quh]], [[1quo]], [[1qsq]], [[261l]], [[262l]], [[259l]], [[220l]], [[222l]], [[223l]], [[225l]], [[226l]], [[227l]], [[228l]], [[229l]], [[235l]], [[236l]], [[237l]], [[238l]], [[239l]], [[240l]], [[241l]], [[242l]], [[243l]], [[244l]], [[245l]], [[246l]], [[247l]], [[248l]], [[249l]], [[250l]], [[251l]], [[252l]], [[253l]], [[254l]], [[255l]], [[230l]], [[231l]], [[232l]], [[233l]], [[234l]], [[209l]], [[210l]], [[211l]], [[212l]], [[213l]], [[214l]], [[215l]], [[218l]], [[219l]], [[180l]], [[195l]], [[196l]], [[197l]], [[198l]], [[199l]], [[200l]], [[190l]], [[191l]], [[192l]], [[189l]], [[155l]], [[156l]], [[157l]], [[158l]], [[159l]], [[160l]], [[161l]], [[162l]], [[163l]], [[164l]], [[165l]], [[166l]], [[129l]], [[130l]], [[131l]], [[140l]], [[141l]], [[142l]], [[143l]], [[144l]], [[145l]], [[146l]], [[147l]], [[201l]], [[205l]], [[221l]], [[224l]], [[102l]], [[103l]], [[104l]], [[107l]], [[108l]], [[109l]], [[110l]], [[111l]], [[112l]], [[113l]], [[114l]], [[115l]], [[118l]], [[119l]], [[120l]], [[122l]], [[123l]], [[125l]], [[126l]], [[127l]], [[128l]], [[1dya]], [[1dyb]], [[1dyc]], [[1dyd]], [[1dye]], [[1dyf]], [[1dyg]], [[1l00]], [[1l85]], [[1l86]], [[1l87]], [[1l88]], [[1l89]], [[1l90]], [[1l91]], [[1l92]], [[1l93]], [[1l94]], [[1l95]], [[1l96]], [[1l97]], [[1l98]], [[1l99]], [[1lye]], [[1lyf]], [[1lyg]], [[1lyh]], [[1lyi]], [[1lyj]], [[217l]], [[1tla]], [[1l77]], [[1l79]], [[1l80]], [[1l81]], [[1l82]], [[2l78]], [[1l36]], [[1l37]], [[1l38]], [[1l39]], [[1l40]], [[1l41]], [[1l42]], [[1l43]], [[1l44]], [[1l45]], [[1l46]], [[1l47]], [[1l48]], [[1l49]], [[1l50]], [[1l51]], [[1l52]], [[1l53]], [[1l54]], [[1l55]], [[1l56]], [[1l57]], [[1l58]], [[1l59]], [[1l60]], [[1l61]], [[1l62]], [[1l63]], [[1l64]], [[1l65]], [[1l66]], [[1l67]], [[1l68]], [[1l69]], [[1l70]], [[1l71]], [[1l72]], [[1l73]], [[1l74]], [[1l75]], [[1l76]], [[1l17]], [[1l18]], [[1l19]], [[1l20]], [[1l21]], [[1l22]], [[1l23]], [[1l24]], [[1l25]], [[1l26]], [[1l27]], [[1l28]], [[1l29]], [[1l30]], [[1l31]], [[1l32]], [[1l33]], [[1l34]], [[1l35]], [[3lzm]], [[1l01]], [[1l02]], [[1l03]], [[1l04]], [[1l05]], [[1l06]], [[1l07]], [[1l08]], [[1l09]], [[1l10]], [[1l11]], [[1l12]], [[1l13]], [[1l14]], [[1l15]], [[1l16]] – T4Lys (mutant) 
[[1c60]], [[1c61]], [[1c62]], [[1c63]], [[1c64]], [[1c65]], [[1c66]], [[1c67]], [[1c68]], [[1c69]], [[1c6a]], [[1c6b]], [[1c6c]], [[1c6d]], [[1c6e]], [[1c6f]], [[1c6g]], [[1c6h]], [[1c6i]], [[1c6j]], [[1c6k]], [[1c6l]], [[1c6m]], [[1c6n]], [[1c6p]], [[1c6q]], [[1c6t]] - T4Lys (mutant) + noble gas 
[[3ht6]], [[3ht7]], [[3ht8]], [[3ht9]], [[3htb]], [[3hu8]], [[3huq]], [[3guj]], [[3guk]], [[3gul]], [[3gum]], [[3gun]], [[3guo]], [[3gup]], [[3dmx]], [[3dmz]], [[3dn0]], [[3dn1]], [[3dn2]], [[3dn3]], [[3dn4]], [[3dn6]], [[3dn8]], [[3dna]], [[2rb1]], [[2ray]], [[2raz]], [[2rb0]], [[2rb2]], [[2rbn]], [[2rbo]], [[2rbq]], [[2rbr]], [[2rbs]], [[2oty]],[[2otz]], [[1owy]], [[1owz]], [[1ov5]], [[1ov7]], [[1ovh]], [[1ovj]], [[1ovk]], [[1lgw]], [[1lgx]], [[1li2]], [[1li3]], [[1l83]], [[1l84]] – T4Lys (mutant) + benzene derivative 
[[3htd]], [[3htf]], [[3htg]], [[3hu9]], [[3hua]], [[3huk]], [[3hh3]], [[3hh4]], [[3hh5]], [[3hh6]], [[2rbp]], [[2ou0]], [[2f2q]], [[2f32]], [[2f47]], [[1xep]] – T4Lys (mutant) + inhibitor 
[[148l]] - T4Lys (mutant) + glucoside 
[[3d3d]], [[1d9u]] – lamLys + chitohexasaccharide 
[[1am7]] – lamLys - Enterobacteria phage λ 
[[2anv]], [[2anx]] – Lys (mutant)]] - Enterobacteria phage p22 
[[1xjt]], [[1xju]] - Lys - Enterobacteria phage p1 
[[1lba]] - T7Lys - Enterobacteria phage T7 

===Lys protein complex===

[[3m18]], [[3g3a]], [[3g3b]] - HEWL + Variable lymphocyte receptor – Marine lamprey 
[[3a67]], [[3a6b]], [[3a6c]], [[2yss]], [[2eiz]], [[2dqc]], [[2dqd]], [[2dqe]], [[2dqf]], [[2dqg]], [[2dqh]], [[2dqi]], [[2dqj]], [[1j1o]], [[1j1p]], [[1j1x]], [[1ic4]], [[1ic5]], [[1ic7]] – HEWL + mLys antibody HYHEL-10 (mutant) 
[[1xgp]], [[1xgq]], [[1xgr]], [[1xgt]], [[1xgu]] – HEWL + mLys antibody HYHEL-63 
[[3d9a]], [[2eks]], [[1ua6]], [[1c08]], [[3hfm]] – HEWL + mLys antibody HYHEL-10 
[[1uac]] - tuLys C + mLys antibody HYHEL-10 
[[1yqv]], [[2iff]] – HEWL + mLys antibody HYHEL-5 
[[1bql]] – BqLys + mLys antibody HYHEL-5 
[[1ndg]] – HEWL + mLys antibody HYHEL-8 
[[1ndm]] – HEWL + mLys antibody HYHEL-26 
[[1dqj]] - HEWL + mLys antibody HYHEL-63 
[[1nby]], [[1nbz]] – HEWL (mutant) + mLys antibody HYHEL-63 
[[1g7h]], [[1g7i]], [[1g7j]], [[1g7l]], [[1g7m]], [[1kip]], [[1kiq]], [[1kir]] – HEWL + mAnti-HEWL monoclonal antibody (mutant) 
[[1mlc]], [[1vfb]] - HEWL + mIGG1-κ D44.1 FAB 
[[1a2y]] - HEWL (mutant) + mIGG1-κ D1.3 FV 
[[1fdl]] - HEWL + mIGG1-κ D1.3 FAB 
[[1jhl]] – phLys + mIGG1-κ D11.15 FV 
[[1fbi]] – GfLys + mIGG1 F9.13.7 FAB 
[[2znw]], [[2znx]] – HEWL + hSCFV10 antibody 
[[1bvk]] - HEWL + hAnti Lys FV antibody 
[[1dzb]] – tuLys + mSCFV 1F9 
[[1zv5]], [[1zvh]], [[1zvy]], [[1zmy]], [[1ri8]], [[1rjc]], [[1xfp]], [[1jtp]], [[1jtt]], [[1jto]], [[1mel]] - HEWL + cAntibody heavy chain domain – camel 
[[1op9]] - hLys C + cAntibody heavy chain domain 
[[3otp]] – HEWL + EcProtease DO – ''Escherichia coli'' 
[[3f6z]] - HEWL + MLIC – ''Pseudomonas aeruginosa'' 
[[3eba]] – hLys C + hCABHUL6 
[[2qb0]], [[2qar]] – T4Lys/E80 TELSAM domain 
[[2i25]], [[2i26]] - HEWL +NsAntigen receptor PBLA8 variable domain – Nurse shark 
[[1sq2]], [[1t6v]] – HEWL +NsNew Antigen receptor variable domain 
[[1gpq]] – HEWL + EcInhibitor of Vertebrate Lys 
[[1aro]] – T7Lys + T7 RNA polymerase 

===Some Useful External Links===
[http://en.wikipedia.org/wiki/Lysozyme Lysozyme]

[http://en.wikipedia.org/wiki/Glycoside_hydrolase#Retaining_glycoside_hydrolases Retaining Glycoside Hydrolases]

===References===
<references/>

Hen Egg-White (HEW) Lysozyme

2011-04-20T17:59:26Z

Anne Goodling:

'''Introduction'''

Lysozyme - also known as muramidase, or glycoside hydrolase - is a powerful enzyme of biological significance found in abundance in tears, saliva, and human milk. In humans, it is encoded in the ''LYZ'' gene. Although it is responsible for the initial digestion of starches in the mouth, it is most widely identified as a non-specific defense in gram positive bacteria and in many species of fungi. Due to its antibacterial effects, it is a strong component of the innate immune system, and is an important part of an infant's diet to ward off diarrheal diseases. Since it is a small, easily available, and highly stable protein containing only 129 amino acid residues, it has been subject to extensive research regarding its function and structure. Hen Egg White (HEW) Lysozyme is shown below.

===History===

Lysozyme is an enzyme known for its unique ability to degrade the polysaccharide architecture of many kinds of cell walls, normally for the purpose of protection against bacterial infection<ref>Lysozyme. 2010. Citizendium.org. http://en.citizendium.org/wiki/Lysozyme</ref>. Its effects were first noticed by Laschtschenko in 1909. It was officially characterized and termed “lysozyme” by Alexander Fleming, the same person credited for the accidental discovery of penicillin.
The characterization of lysozyme in 1922 by Alexander Fleming was providential in that the undertaken experiment related to the discovery of lysozyme was not geared toward any knowledge of such a protein as lysozyme <ref>Lysozyme. 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>. During the unrelated experiment, nasal drippings were inadvertently introduced to a petri dish containing a bacterial culture, which culture consequently exhibited the results of an as yet unknown enzymatic reaction. The observation of this unknown reaction led to further research on the components of this reaction as well as to the corresponding identification of the newfound "lysozyme." Fleming's discovery was complemented by David C. Phillips' 1965 description of the three-dimensional structure of lysozyme via a 200 pm resolution model obtained from X-ray crystallography <ref>Lysozyme, 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>. Phillips' work was especially groundbreaking since Phillips had managed to successfully elucidate the structure of an enzyme via X-ray crystallography - a feat that had never before been accomplished<ref>Bugg, T. 1997. An Introduction to Enzyme and Coenzyme Chemistry. Blackwell Science Ltd., Oxford </ref>. Phillips' research also led to the first sufficiently described enzymatic mechanism of catalytic action <ref>1967. Proc R Soc Lond B Bio 167 (1009): 389–401.</ref>. Thus, Phillips' elucidation of the function of lysozyme led Phillips to reach a more general conclusion on the diversity of enzymatic chemical action in relation to enzymatic structure. Clearly, the findings of Phillips as well as the more general historical development of the understanding of the structure and function of lysozyme have been paramount to the more general realm of enzyme chemistry.

[[Image:nag-nam2.jpg|thumb|left|350px|Lysozyme Cleavage Site]]
<ref>Image from: http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/proteins/lysozyme.htm</ref>

'''Function'''

Lysozyme is known for damaging bacterial cell walls by catalyzing the hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid (NAM) and N-acetyl-D-glucosamine (NAG) residues in peptidoglycan, and between N-acetyl-D-glucosamine residues in chitodextrins. In this way, lysozyme is efficient in lysing the cell walls of both bacteria and fungi. The location of cleavage for lysozyme on this architectural theme is the β(1-4) glycosidic linkage connecting the C1 carbon of NAM to the C4 carbon of NAG.

The particular substrate of preference for this cleavage type is a (NAG-NAM)₃ hexasaccharide, within which substrate occurs the
cleaving target glycosidic bond, NAM₄-β-O-NAG₅. The individual hexasaccharide binding units are designated A-F, with NAM₄-β-O-NAG₅ glycosidic bond cleavage preference corresponding to a D-E unit glycosidic bond cleavage preference.

= Enzymatic Activity of Lysozyme =

Enzymes are designed to attract and to bind specific substrates. The active site of and lysozyme and its specific ligands are described in the following sections

==Mechanistic Features==

'''Zymogen of Lysozyme: Enzymatic Precursor'''

Zymogens are inactive enzyme precursors. Enzymes are developed in an inactive way to prevent the enzyme from digesting the cell that produced it. This process also prevents the enzyme from becoming active in the wrong portion of the body. Lysozyme's zymogen, simply titled “pre-lysozyme,” was sequenced in 1977 by R D Palmiter, J Gagnon, L H Ericsson and K A Walsh, and has since been sequenced much more extensively.

[[Image:jrip.jpg|thumb|left|350px|Mechanism of Lysozyme]]
<ref>Image from: http://www.google.com/imgres?imgurl=http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/pics-and-strucs/lysozyme-mech.gif&imgrefurl=http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/proteins/lysozyme.htm&usg=__ormapG4XKg-tR5GrMSOdSMTV4vE=&h=603&w=801&sz=7&hl=en&start=17&zoom=1&tbnid=nvr9gvFrUILDkM:&tbnh=143&tbnw=189&prev=/images%3Fq%3DThe%2Blysozyme%2Breaction%2Bmechanism%26um%3D1%26hl%3Den%26sa%3DN%26biw%3D1280%26bih%3D647%26tbs%3Disch:10%2C304&um=1&itbs=1&iact=hc&vpx=521&vpy=349&dur=448&hovh=191&hovw=254&tx=140&ty=48&ei=JQ_LTPKzLIjCsAPkzt2KDg&oei=IA_LTP74OsG78gapm-GFAQ&esq=2&page=2&ndsp=18&ved=1t:429,r:2,s:17&biw=1280&bih=647</ref>

'''Mechanism'''

The lysozyme mechanism of action results in the hydrolysis of a glycoside (hence the familial distinction of lysozyme as a glycosylase<ref>Lysozyme, 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>), which corresponds to the conversion of an acetal to a hemiacetal, which reaction (general degradation of glycosidic bond to units "capped" by newly formed hydroxyl groups) necessitates acid catalysis, since the conversion of acetal to hemiacetal involves the protonation of the reactant oxygen prior to actual bond cleavage. <ref>Pratt, C.W., Voet, D., Voet, J.G. Fundamentals of Biochemistry - Life at the Molecular Level - Third Edition. Voet, Voet and Pratt, 2008.</ref>. Furthermore, the transition state obtained from this protonation is a covalent, oxonium ion, intermediate that must obtain resonance stabilization. The need for some means of acid catalysis and covalent resonance stabilization is adequately provided by the Glu 35 and Asp 52 residues of lysozyme, respectively. The reaction mechanism of lysozyme is demonstrated below. In the following image, the reaction begins at the upper left-hand side, and proceeds according to reaction arrows.

As seen to the left, lysozyme works by hydrolyzing the glycosidic bond, distorting the bond between the NAM and NAG. This produces a glycosyl enzyme intermediate, which reacts with a water molecule to produce the product and the unchanged enzyme.

'''Active Site'''

The <scene name='Hen_Egg-White_(HEW)_Lysozyme/Act_site/2'>active site</scene> of lysozyme is formulated as a prominent cleft outlined by the two aforementioned catalytic amino acids, Glu 35 and Asp 52. The active site is geometrically bent to augment ligand binding, and the two amino acids interact with the ligand in the binding site. Asp52 is depicted in red, and Glu35 is depicted in green.

<applet load='1hew' size='350' frame='true' align='right' caption='' />

==Binding==
'''Ligands'''

A <scene name='Sandbox_39/Ligands_1/1'>ligand</scene> is able to bind to the active site of an enzyme to form a biologically relevant complex. The model to the right shows a space-filling model of lysozyme with the protein distinguishable in brown and the ligand distinguishable in green. Another model of the ligand can be seen in this
<scene name='Sandbox_39/Ribbon_ligand/1'>ribbon diagram</scene>, with the ligand protruding as a space-filling model from the active site. Here, it is clear that the ligand is a polysaccharide.

The lysozyme reaction is characterized by hydrolysis of the beta (1-4) glycosidic bond between NAM and NAG. Lysozyme has a very specific active site, which can bind only six sugar rings from a polysaccharide chain. Once lysozyme binds to this chain, it hydrolyzes them. These six sugar rings represent the ligand of lysozyme. The lysozyme then distorts the fourth sugar in the six-membered complex, producing stress on the molecule and breaking the glycosidic bond.

The amino acid side-chains Glu35 and Asp52 are critical to the activity of this enzyme. Glu35 acts as a proton donor to the glycosidic bond, cleaving the C-O bond in the substrate, and Asp52 acts as a nucleophile to generate a glycosyl enzyme intermediate. The glycosyl enzyme intermediate then reacts with a water molecule to give the product of hydrolysis.

'''Inhibitors'''

Lysozyme is best inhibited by small saccharides which act competitively with the natural substrate. The smaller saccharides will bind to the first three binding sites of the cleft (sites A-C), but will not reach sites D and E, where the enzyme cuts the glycosidic bond. So, the competitive inhibitor will stick in the cleft, not allowing the substrate to bind to the enzyme complex.<ref>http://mcdb-webarchive.mcdb.ucsb.edu/sears/biochemistry/tw-enz/lysozyme/HEWL/lysozyme-overview.htm</ref> Several known inhibitors of lysozyme are: SDS, N-acetyl-D-glucosamine, and various alcohols and oxidizing agents.<ref>http://www.worthington-biochem.com/ly/default.html</ref>

<applet load='1hew' size='350' frame='true' align='left' caption='' />

= Composition and Structure of Lysozyme =

All proteins consist of carbon, hydrogen, nitrogen, oxygen, and sulfur, as do most organic molecules. Enzymes are composed in such a way as to maximize their reactivity with their desired substrate, increasing the efficiency of biological reactions. The <scene name='Sandbox_39/Elements/1'>composition of lysozyme</scene> can be seen on the left, with the carbon atoms outlined in gray, oxygen atoms in red, nitrogen atoms in blue, sulfur atoms in yellow, and the three-letter abbreviation for the <scene name='Sandbox_39/Amino_acid_residues/1'>amino acid residues</scene> in purple.

Lysozyme, like all proteins, also contains a <scene name='Sandbox_39/C_and_n_terminal_residues/1'> 3'C and 5'N terminal </scene>, and these can be seen by following the colors of the rainbow across the molecule. Starting at the red end, the 3' C terminal end, one can work the entire way through to the 5' N terminal end, showing the folding pattern and chain of the protein.

== Secondary Structure ==

Lysozyme contains five <scene name='Sandbox_38/A/2'>alpha helical</scene> regions and five regions containing <scene name='Sandbox_38/B/1'>beta sheets</scene> as displayed in this <scene name='Sandbox_38/Alphab/1'>image</scene>. Linking these secondary structures, a number of beta turns and a large number of random coils make up the remainder of the polypeptide backbone. The polypeptide backbone of lysozyme involved in the 3 antiparallel beta sheets display the beta hairpin motif of supersecondary structure. This depiction of lysozyme contains an antiparallel beta-pleated sheet, which contributes greatly to the stability of the molecule by providing the correct alignment of hydrogen bonds. Lysozyme also contains a great deal of random coil, which is seen in the white regions of the molecule.

==Amino Acid Residues==

The amino acids present in the lysozyme polypeptide sequence have a direct influence not only on primary structure, but also on the secondary and tertiary structures, which can be influenced by polarity and charge of the sidechains. The various amino acid <scene name='Sandbox_38/Aminoi/1'>residues</scene> differ in their properties because of the great variety of side chains present on each amino acid. Polar and nonpolar (and charged and uncharged) side chains lead to various degrees of hydrophobicity and hydrophilicity, which affects protein folding. In lysozyme, these <scene name='Sandbox_38/Sc/1'>side chains</scene> are displayed for each amino acid residue.

= Bonding Interactions =

'''Disulfide Bonding in Lysozyme'''

Lysozyme contains four <scene name='Sandbox_39/Disulfide_bonds/1'>disulfide bonds</scene> involving eight cysteine residues, which are highlighted in yellow on the left. Disulfide bonds are intramolecular forces that stabilize the tertiary structure of many proteins. Disulfide bonds are present in four locations in lysozyme: between Cys 6 and Cys 127, between Cys 30 and Cys 115, between Cys 64 and Cys 80 and between Cys 76 and Cys 94.

'''Hydrogen Bonding'''

In all proteins <scene name='Sandbox_39/Hydrogen_bonds/2'>hydrogen bonds</scene> are essential for stability. In this ribbon diagram, the hydrogen bonds can be seen between the secondary structures of lysozyme highlighted in orange. Since the double bonds of the alpha carbons in the main chain of lysozyme cause torsional strain, lysozyme is limited to very specific hydrogen bonding between the amino acid residues. This representation clearly shows how crucial hydrogen bonding is to help maintain the stability of the protein.

<applet load='1hew' size='350' frame='true' align='left' caption='' />

= Intermolecular Interactions =

'''Hydrophobicity'''

Lysozyme contains both hydrophobic and hydrophilic regions ( <scene name='Sandbox_39/Hydrophobicity/2'>Hydrophobicity</scene> ). The hydrophilic effect, or the desire for proteins to be at a specific position regarding water, is the single most important determinant of protein folding. These regions can be displayed with the hydrophobic regions in gray and the polar, hydrophillic regions in purple. This coloration highlights the location of these regions, showing that the majority of the hydrophobic regions are inside of the protein and that the majority of the hydrophillic regions are on the outside of the protein.

'''Polarity'''

The nature of the amino acid sidechains in the lysozyme polypeptide sequence leads to regions of varying hydrophobicities and polarities of the enzyme structure. The presence of certain regions of hydrophilicity and hydrophobicity is a driving force in determining protein structure when folding. The varying polarities of the side chains influence the locations of residues in the enzyme structure. Nonpolar residues appear blue, and polar residues appear red in the following <scene name='Sandbox_38/Non_polar_blue/1'>polarity</scene> display of lysozyme. Nonpolar residues will display hydrophobic tendencies occurring mostly on the interior of the enzyme while polar residues will increase in abundance on the surface of the protein in order to increase contact with the aqueous solvent so as to satisfy their hydrophilic nature. By observing a space-filled structural depiction of <scene name='Sandbox_38/Non_polar_blu/1'>lysozyme polarity</scene> with polar molecules colored red and nonpolar molecules colored blue the influence of polarity on nucleotide arrangement and protein folding is evident, with the blue (nonpolar) regions inside the red (polar) regions. The presence of <scene name='Sandbox_39/Water/1'>water</scene> interacting with the various hydrophilic residues is depicted to further display how polarity affects structure. Water is depicted as yellow, and the polar and nonpolar regions remain their respective color.

'''Charge'''

Charges of the various regions of the lysozyme structure display a hydrophilic nature and thus also affect the location of that region of polypeptides and the overall folding of the protein. Charged regions of the protein will display hydrophilic tendencies and therefore will most often be located on the surface of the lysozyme molecule where they can interact with the aqueous solvent. Non-charged portions will display hydrophobic tendencies and be located on the interior of the molecule. The effect of various <scene name='Sandbox_38/Rb/1'>charges</scene> on protein structure can be visualized with charged molecules represented by red anionic and blue cationic regions, and uncharged regions colored in grey. This depiction of lysozyme uses a spacefill representation of lysozyme to depict <scene name='Sandbox_38/Chargeddd/1'>charges</scene>.

= Applications of Lysozyme =

Since lysozyme has been widely recognized for its antibacterial and antifungal properties, it has a wide variety of uses both in biochemical and pharmaceutical applications. In molecular biology, lysozyme is often used in the alkaline-lysis procedure for extracting and isolating plasmid DNA. It is used extensively in the pharmaceutical field for destroying gram-positive bacteria, and can be used to support already-existing immune defenses to fight bacterial infections. This enzyme is particularly important for preventing bacterial diseases in infants. Because of its antibacterial properties, lysozyme can also be used in the food industry to help prevent spoilage of foods.

= Discovery and Applications of Hen Egg-White Lysozyme=

<applet load='aln_1H6M_to_1HEW_2.pdb' size='300' frame='true' align='right' caption=' Hen Egg White (HEW) Lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to the active site, PDBid 1HEW' scene='User:Judy_Voet/Lysozyme/Lysozyme1/16' />
Lysozyme was the first enzyme whose X-ray structure was determined <ref> PMID 5840126</ref><ref>Phillips, D. C. The hen egg white lysozyme molecule. Proc. Natl Acad. Sci. USA 57, 483-495 (1967)</ref>. This <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>scene </scene> shows Hen Egg White (HEW) lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to a cleft in the enzyme. David Phillips, who determined the structure in 1965, saw that the cleft was large enough to fit three more saccharide units.
He therefore built a model extending the trisaccharide to a
<scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> that fits into the cleft, labeling the sugar subsites A-F<ref> coordinates of the model kindly provided by Louise Johnson</ref>. Alternately click on <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>trisaccharide</scene> and <scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> to turn the modeled portion of the hexasaccharide on and off.

The interesting thing about the model was that the only way that the hexasaccharide would fit into the cleft was if the 4th saccharide (in subsite D) was strained into a <scene name='User:Judy_Voet/Lysozyme/Half-chair/2'>half-chair conformation</scene>. This conformation is what would be necessary for the formation of an oxocarbenium ion (oxionium ion). When the model was studied, <scene name='User:Judy_Voet/Lysozyme/Glu_35/1'>Glu 35</scene> was found to be in an ideal location to act as a general acid catalyst, 3.34 Angstroms from the bridging oxygen between the 4th and 5th saccharide units. <scene name='User:Judy_Voet/Lysozyme/Asp_52/2'>Asp 52</scene> appeared to be too far away (2.69 angstroms) in the static lysozyme structure to have formed a covalent bond with C1 of the half-chair model in the D site, and no covalent intermediate had ever been detected, so Phillips proposed that it acted as an electrostatic stabilizer of the oxonium ion (referred to as The Phillips Mechanism).

<applet load='aln_1H6M_to_1HEW_2.pdb' size='200' frame='true' align='left' caption='NAG-2-deoxy-2-fluoro-glucosyl fluoride (NAG2FGlcF) bound to Glu35Gln HEW Lysozyme PDBid 1H6M' scene='User:Judy_Voet/Lysozyme/1h6m/3'/>

Then, in 2001, Stephen Withers published <scene name='User:Judy_Voet/Lysozyme/1h6m/3'>1H6M</scene>,<ref>PMID 11518970</ref> in which Glu 35 had been mutated to Gln to remove the general acid catalyst. The substrate contained NAG-2-fluoro-glucosyl fluoride (NAG2FGlcF). The fluoro group on C-1 does not require acid catalysis to be a good leaving group, and the remaining saccharide, in the absence of the acid necessary to catalyse the second step of the reaction, was demonstrated to form a <scene name='User:Judy_Voet/Lysozyme/Covalent/1'> covalent intermediate</scene>. In this <scene name='User:Judy_Voet/Lysozyme/Superposition/2'>superposition</scene> of the half chair model with 1HEW (greens) and the covalent intermediate in 1H6M (blues), note the relatively small motions of Asp 52 and C1 of the sugar ring in going from the model to the covalent intermediate. to observe the motion from the <scene name='User:Judy_Voet/Lysozyme/Asp52_halfchair/1'>half-chair</scene> to the <scene name='User:Judy_Voet/Lysozyme/Covalent/2'>covalent intermediate</scene> just toggle between the two green links.

== 3D Structures of Lysozyme ==

===Lys===

[[2x0a]], [[3iju]], [[3ijv]], [[3a8z]], [[2w1y]], [[2w1m]], [[2w1x]], [[2w1l]], [[3e3d]], [[3exd]], [[2zq3]], [[2zq4]], [[3b72]], [[3b6l]], [[2z12]], [[2z18]], [[2z19]], [[2vb1]], [[2hu3]], [[2hub]], [[2htx]], [[2hu1]], [[2yvb]], [[2epe]], [[2g4p]], [[2g4q]], [[2cgi]], [[2b5z]], [[2d4k]], [[2d91]], [[2f2n]], [[2fbb]], [[2c8o]], [[2c8p]], [[2a6u]], [[2aub]], [[2blx]], [[2bly]], [[2a7d]], [[2a7f]], [[1wtm]], [[1wtn]], [[1w6z]], [[1vdp]], [[1vdq]], [[1vds]], [[1vdt]], [[1ved]], [[1v7t]], [[1ps5]], [[2cds]], [[1lj3]], [[1lj4]], [[1lje]], [[1ljf]], [[1ljg]], [[1ljh]], [[1lji]], [[1ljj]], [[1ljk]], [[1jis]], [[1jit]], [[1jiy]], [[1jj0]], [[1jj1]], [[1jj3]], [[1iee]], [[1qio]], [[1f0w]], [[1f10]], [[1dpx]], [[1c10]], [[1qtk]], [[1lz8]], [[1lz9]], [[1bhz]], [[1bgi]], [[1bwh]], [[1bwi]], [[1bwj]], [[1bvx]], [[1hsw]], [[1hsx]], [[1lpi]], [[4lzt]], [[3lzt]], [[1aki]], [[1jpo]], [[1rfp]], [[193l]], [[194l]], [[5lym]], [[1lza]], [[3lyt]], [[4lyt]], [[5lyt]], [[6lyt]], [[2lzt]], [[1lzt]], [[1lzh]], [[2lzh]], [[7lyz]], [[1lyz]], [[2lyz]], [[3lyz]], [[4lyz]], [[5lyz]], [[6lyz]] - HEWL – chicken 
[[1xei]], [[1xej]], [[1xek]], [[1uco]], [[1lma]], [[4lym]] – HEWL low hydration 
[[1lsa]], [[1lsb]], [[1lsc]], [[1lsd]], [[1lse]], [[1lsf]], [[1lys]] – HEWL temperature influence 
[[2lym]], [[3lym]] – HEWL pressure influence 
[[132l]] – HEWL methylated 
[[1rcm]] – HEWL 3 S-S form 
[[2xbr]], [[2xbs]]- HEWL– Raman crystallography 
[[2zwb]], [[1io5]], [[1lzn]] - HEWL– Neutron 
[[1gxv]], [[1gxx]], [[1e8l]] - HEWL- NMR 
[[2hs7]], [[2hso]], [[2hs9]]- HEWL– Powder diffraction 
[[1ir7]], [[1ir8]], [[1ir9]], [[1ioq]], [[1ior]], [[1ios]], [[1iot]], [[1flq]], [[1flu]], [[1flw]], [[1fly]], [[1fn5]], [[1kxw]], [[1kxx]], [[1kxy]], [[1uia]], [[1uib]], [[1uic]], [[1uid]], [[1uie]], [[1uif]], [[1uig]], [[1uih]], [[1lsm]], [[1lsn]], [[1hel]], [[1hem]], [[1hen]], [[1heo]], [[1hep]], [[1heq]], [[1her]] – HEWL (mutant) 
[[1lyo]], [[2lyo]], [[3lyo]], [[4lyo]] – HEWL cross-linked 
[[1xft]] - tuLys – turkey - Powder diffraction 
[[1jse]], [[1tew]], [[135l]], [[2lz2]], [[1lz2]] – tuLys 
[[3lz2]] – tuLys - Laue 
[[3ab6]] – Lys + NAG3 – Hard clam 
[[2x8r]] – Lys GH25 – ''Aspergillus fumigatus'' 
[[3mgw]] – Lys G – Atlantic salmon 
[[3gxk]], [[3gxr]] – Lys G + NAG – Atlantic cod 
[[2fbd]] – HfLys 1 
[[3cb7]] – HfLys 2 
[[2zij]], [[2zik]], [[2zil]], [[2nwd]], [[1iwt]], [[1iwu]], [[1iwv]], [[1iww]], [[1iwx]], [[1iwy]], [[1iwz]], [[1jwr]], [[1jsf]], [[1rex]], [[1lz1]] – hLys – human 
[[1w08]], [[1ix0]], [[1ioc]], [[1ip1]], [[1ip2]], [[1ip3]], [[1ip4]], [[1ip5]], [[1ip6]], [[1ip7]], [[1qsw]], [[1gev]], [[1gez]], [[1gf0]], [[1gf3]], [[1gf4]], [[1gf5]], [[1gf6]], [[1gf7]], [[1i1z]], [[1i20]], [[1i22]], [[1gfr]], [[1gft]], [[1gfu]], [[1gfv]], [[1gf8]], [[1gf9]], [[1gfa]], [[1gfe]], [[1gfg]], [[1gfh]], [[1gfj]], [[1gfk]], [[1inu]], [[1gdx]], [[1ge0]], [[1ge1]], [[1ge2]], [[1ge3]], [[1ge4]], [[1gdw]], [[1gaz]], [[1gb0]], [[1gb2]], [[1gb3]], [[1gb5]], [[1gb6]], [[1gb7]], [[1gb8]], [[1gb9]], [[1gbo]], [[1gbw]], [[1gbx]], [[1gby]], [[1gbz]], [[1gay]], [[1eq4]], [[1eq5]], [[1eqe]], [[1c7p]], [[1di3]], [[1di4]], [[1di5]], [[1c43]], [[1c45]], [[1c46]], [[1ckg]], [[1cj6]], [[1cj7]], [[1cj8]], [[1cj9]], [[1ckc]], [[1ckd]], [[1ckf]], [[1ckh]], [[1b5z]], [[1b70]], [[1b7q]], [[1b7r]], [[1b7s]], [[1b7l]], [[1b7m]], [[1b7n]], [[1b7p]], [[1b5u]], [[1b5v]], [[1b5w]], [[1b5x]], [[1b5y]], [[1bb3]], [[1bb4]], [[2bqa]], [[2bqb]], [[2bqc]], [[2bqd]], [[2bqe]], [[2bqf]], [[2bqg]], [[2bqh]], [[2bqi]], [[2bqj]], [[2bqk]], [[2bql]], [[2bqm]], [[2bqn]], [[2bqo]], [[2mea]], [[2meb]], [[2mec]], [[2med]], [[2mee]], [[2mef]], [[2meg]], [[2meh]], [[2mei]], [[1wqm]], [[1wqn]], [[1wqo]], [[1wqp]], [[1wqq]], [[1wqr]], [[2heb]], [[2hea]], [[2hec]], [[2hed]], [[2hee]], [[2hef]], [[1jka]], [[1jkb]], [[1jkc]], [[1jkd]], [[1loz]], [[1lyy]], [[1oua]], [[1oub]], [[1ouc]], [[1oud]], [[1oue]], [[1ouf]], [[1oug]], [[1ouh]], [[1oui]], [[1ouj]], [[207l]], [[208l ]], [[1yam]], [[1yan]], [[1yao]], [[1yap]], [[1yaq]], [[1lmt]], [[1lhh]], [[1lhi]], [[1lhj]], [[1lhk]], [[1lhl]], [[133l]], [[134l]], [[1lz4]], [[1lz5]], [[1lz6]], [[1laa]], [[1tay]], [[1tby]], [[1tcy]], [[1tdy]], [[2lhm]], [[3lhm]] – hLys (mutant) 
[[1iy3]], [[1iy4]] – hLys - NMR 
[[2z2f]] – Lys – Bovine 
[[2cwi]], [[1el1]], [[1qqy]] – dLys - dog 
[[2z2e]] – dLys (mutant) 
[[1i56]] – dLys – NMR 
[[2dqa]] – Lys – ''Tapes japonica'' 
[[2gv0]] – Lys – Soft-shelled turtle 
[[1ivm]] – mLys M – NMR – mouse 
[[1jfx]] – Lys – ''Streptomyces coelicolor'' 
[[1gd6]] – Lys – ''Bombyx mori'' 
[[1jug]] – Lys – Echidna 
[[1dkj]] – BqLys – Bobwhite quail 
[[2ihl]] – Lys – Japanese quail 
[[1gbs]] – BsLys – Black swan 
[[1lmn]] – RtLys – Rainbow trout 
[[2eql]] – Lys – horse 
[[1ghl]] – phLys – pheasant 
[[1hhl]] – GfLys – Guinea fowl 
[[1lhm]] – Lys (mutant) – yeast 

===Lys small molecules complexes===

[[3fe0]], [[2d4i]], [[2d4j]], [[1v7s]] - HEWL+ D2O 
[[3m3u]] – HEWL Trp fluorescence 
[[2xjw]] - HEWL + CO 
[[1hf4]], [[1lks]] – HEWL + NO3 
[[3a34]], [[3ems]] - HEWL + arginine 
[[2xth]] – cLys + inhibitor K2PtBr6 
[[3a90]], [[3a91]], [[3a92]], [[3a93]], [[3a94]], [[3a95]], [[3a96]], [[3kam]], [[2pc2]], [[2bpu]], [[1t3p]], [[1h87]] – HEWL + rare earth 
[[2d6b]], [[2hg0]], [[1vat]], [[1gwd]], [[1b2k]], [[1lkr]], [[1azf]], [[8lyz]]- HEWL+ halogen 
[[1vat]] - HEWL + Xe 
[[1n4f]] - HEWL + As 
[[2i6z]] - HEWL + Pt drug 
[[2zyp]] - HEWL + poly (allyl amine) 
[[2f30]], [[2f4a]] – HEWL + urea derivative 
[[2f4g]], [[1ykx]], [[1yky]], [[1ykz]], [[1yl0]], [[1yl1]], [[1z55]] - HEWL + alcohol 
[[1dpw]] – HEWL + MPD 
[[1lcn]] – HEWL + SCN 
[[2zxs]] - HEWL with glycine-amide 
[[2h9j]], [[2h9k]], [[1yik]], [[1yil]] - HEWL + cyclam derivative 
[[1b0d]] – HEWL + p-toluene-sulfonate 
[[2q0m]] - HEWL + tricarbonylmanganese 
[[2war]] – HEWL (mutant) + chitopentaose 
[[2h5z]] – HfLys 1 + chitotetraose – House fly 
[[1hnl]] – hLys + glutathione 
[[1dkk]] – BqLys + NO3 

===Lys complex with glucoside===

[[3a3q]] – HEWL (mutant) + NAG 
[[1sf4]], [[1sf6]], [[1sf7]], [[1sfb]], [[1sfg]], [[1ja2]], [[1ja4]], [[1ja6]], [[1ja7]] – HEWL + NAG oligosaccharide – Powder diffraction 
[[1ubz]], [[1d6p]], [[1d6q]], [[1bb5]] – hLys (mutant) + glycoside 
[[1uc0]], [[1re2]], [[1rem]], [[1rey]], [[1rez]], [[1lzr]], [[1lzs]] - hLys + glycoside 
[[1ljn]], [[1jef]], [[1lzy]] – tuLys + glycoside 
[[1h6m]], [[1at5]], [[1at6]], [[1lzb]], [[1lzc]], [[1lzd]], [[1lze]], [[1lzg]], [[1hew ]]– HEWL + glycoside 
[[1lsy]], [[1lsz]] - HEWL (mutant) + glycoside 
[[1bb6]], [[1bb7]] – RtLys + glycoside 
[[1lmc]] – RtLys + bulgecin 
[[1lmo]], [[1lmp]], [[1lmq]] – RtLys + glucoside 
[[1lsp]] – BsLys + bulgecin 
[[153l]], [[154l]] – Lys +glucoside – goose 

===Phage Lys===

[[2oe4]], [[2oe7]], [[2oe9]], [[2oea]], [[1swz]], [[1cx6]], [[1qtc]], [[1qtd]], [[1qth]], [[1qsb]], [[1qs5]], [[1qs9]], [[1qtb]], [[256l]], [[206l]], [[167l]], [[168l]], [[169l]], [[170l]], [[171l]], [[172l]], [[173l]], [[174l]], [[175l]], [[176l]], [[177l]], [[178l]], [[181l]], [[182l]], [[183l]], [[184l]], [[185l]], [[186l]], [[187l]], [[188l]], [[1nhb]], [[137l]], [[216l]], [[152l]], [[149l]], [[150l]], [[151l]], [[1lyd]], [[2lzm]] - T4Lys – Enterobacteria phage T4 
[[138l]] – T4Lys cross-linked 
[[4lzm]], [[5lzm]], [[6lzm]], [[7lzm]] – T4Lys ionic strength 
[[3l2x]], [[3k2r]], [[3g3v]], [[3g3w]], [[3g3x]], [[2q9d]], [[2q9e]], [[2igc]], [[2ntg]], [[2nth]], [[2ou8]], [[2ou9]], [[1zur]], [[1zwn]], [[1zyt]], [[2cuu]], [[2a4t]] – T4Lys (mutant) spin labeled 
[[3l64]], [[3hwl]], [[3jr6]], [[3gui]], [[3c7w]], [[3c7y]], [[3c7z]], [[3c80]], [[3c81]], [[3c82]], [[3c83]], [[3c8q]], [[3c8r]], [[3c8s]], [[3cdo]], [[3cdq]], [[3cdr]], [[3cdt]], [[3cdv]], [[3f8v]], [[3f9l]], [[3fa0]], [[3fad]], [[3fi5]], [[3dke]], [[3dmv]], [[2o4w]], [[2o79]], [[2o7a]], [[2huk]], [[2hul]], [[2hum]], [[2b7x]], [[2b6t]], [[2b6w]], [[2b6x]], [[2b6y]], [[2b6z]], [[2b70]], [[2b72]], [[2b73]], [[2b74]], [[2b75]], [[1sx7]], [[1swy]], [[1sx2]], [[1t6h]], [[1ssw]], [[1ssy]], [[1t8f]], [[1t8g]], [[1t8a]], [[1t97]], [[1p56]], [[1p5c]], [[1p2l]], [[1p2r]], [[1p36]], [[1p37]], [[1p3n]], [[1p46]], [[1p64]], [[1p6y]], [[1p7s]], [[1pqd]], [[1pqi]], [[1pqj]], [[1pqk]], [[1pqm]], [[1pqo]], [[1oyu]], [[1ks3]], [[1kw5]], [[1kw7]], [[1ky0]], [[1ky1]], [[1l0j]], [[1l0k]], [[1lw9]], [[1lwg]], [[1lwk]], [[1lpy]], [[1llh]], [[1lgu]], [[1li6]], [[1jtm]], [[1jtn]], [[1jqu]], [[1kni]], [[1g06]], [[1g07]], [[1g0g]], [[1g0j]], [[1g0k]], [[1g0l]], [[1g0m]], [[1g0p]], [[1g0q]], [[1g1v]], [[1g1w]], [[1i6s]], [[257l]], [[258l]], [[260l]], [[1epy]], [[1b6i]], [[1cu6]], [[1d9w]], [[1ctw]], [[1cu0]], [[1cu2]], [[1cu3]], [[1cu5]], [[1cv1]], [[1cv4]], [[1cv5]], [[1cv6]], [[1cvk]], [[1cx7]], [[1d2w]], [[1d2y]], [[1d3f]], [[1d3j]], [[1d3m]], [[1d3n]], [[1cv3]], [[1qt3]], [[1qt4]], [[1qt5]], [[1qt6]], [[1qt7]], [[1qt8]], [[1qtv]], [[1qtz]], [[1qud]], [[1qug]], [[1quh]], [[1quo]], [[1qsq]], [[261l]], [[262l]], [[259l]], [[220l]], [[222l]], [[223l]], [[225l]], [[226l]], [[227l]], [[228l]], [[229l]], [[235l]], [[236l]], [[237l]], [[238l]], [[239l]], [[240l]], [[241l]], [[242l]], [[243l]], [[244l]], [[245l]], [[246l]], [[247l]], [[248l]], [[249l]], [[250l]], [[251l]], [[252l]], [[253l]], [[254l]], [[255l]], [[230l]], [[231l]], [[232l]], [[233l]], [[234l]], [[209l]], [[210l]], [[211l]], [[212l]], [[213l]], [[214l]], [[215l]], [[218l]], [[219l]], [[180l]], [[195l]], [[196l]], [[197l]], [[198l]], [[199l]], [[200l]], [[190l]], [[191l]], [[192l]], [[189l]], [[155l]], [[156l]], [[157l]], [[158l]], [[159l]], [[160l]], [[161l]], [[162l]], [[163l]], [[164l]], [[165l]], [[166l]], [[129l]], [[130l]], [[131l]], [[140l]], [[141l]], [[142l]], [[143l]], [[144l]], [[145l]], [[146l]], [[147l]], [[201l]], [[205l]], [[221l]], [[224l]], [[102l]], [[103l]], [[104l]], [[107l]], [[108l]], [[109l]], [[110l]], [[111l]], [[112l]], [[113l]], [[114l]], [[115l]], [[118l]], [[119l]], [[120l]], [[122l]], [[123l]], [[125l]], [[126l]], [[127l]], [[128l]], [[1dya]], [[1dyb]], [[1dyc]], [[1dyd]], [[1dye]], [[1dyf]], [[1dyg]], [[1l00]], [[1l85]], [[1l86]], [[1l87]], [[1l88]], [[1l89]], [[1l90]], [[1l91]], [[1l92]], [[1l93]], [[1l94]], [[1l95]], [[1l96]], [[1l97]], [[1l98]], [[1l99]], [[1lye]], [[1lyf]], [[1lyg]], [[1lyh]], [[1lyi]], [[1lyj]], [[217l]], [[1tla]], [[1l77]], [[1l79]], [[1l80]], [[1l81]], [[1l82]], [[2l78]], [[1l36]], [[1l37]], [[1l38]], [[1l39]], [[1l40]], [[1l41]], [[1l42]], [[1l43]], [[1l44]], [[1l45]], [[1l46]], [[1l47]], [[1l48]], [[1l49]], [[1l50]], [[1l51]], [[1l52]], [[1l53]], [[1l54]], [[1l55]], [[1l56]], [[1l57]], [[1l58]], [[1l59]], [[1l60]], [[1l61]], [[1l62]], [[1l63]], [[1l64]], [[1l65]], [[1l66]], [[1l67]], [[1l68]], [[1l69]], [[1l70]], [[1l71]], [[1l72]], [[1l73]], [[1l74]], [[1l75]], [[1l76]], [[1l17]], [[1l18]], [[1l19]], [[1l20]], [[1l21]], [[1l22]], [[1l23]], [[1l24]], [[1l25]], [[1l26]], [[1l27]], [[1l28]], [[1l29]], [[1l30]], [[1l31]], [[1l32]], [[1l33]], [[1l34]], [[1l35]], [[3lzm]], [[1l01]], [[1l02]], [[1l03]], [[1l04]], [[1l05]], [[1l06]], [[1l07]], [[1l08]], [[1l09]], [[1l10]], [[1l11]], [[1l12]], [[1l13]], [[1l14]], [[1l15]], [[1l16]] – T4Lys (mutant) 
[[1c60]], [[1c61]], [[1c62]], [[1c63]], [[1c64]], [[1c65]], [[1c66]], [[1c67]], [[1c68]], [[1c69]], [[1c6a]], [[1c6b]], [[1c6c]], [[1c6d]], [[1c6e]], [[1c6f]], [[1c6g]], [[1c6h]], [[1c6i]], [[1c6j]], [[1c6k]], [[1c6l]], [[1c6m]], [[1c6n]], [[1c6p]], [[1c6q]], [[1c6t]] - T4Lys (mutant) + noble gas 
[[3ht6]], [[3ht7]], [[3ht8]], [[3ht9]], [[3htb]], [[3hu8]], [[3huq]], [[3guj]], [[3guk]], [[3gul]], [[3gum]], [[3gun]], [[3guo]], [[3gup]], [[3dmx]], [[3dmz]], [[3dn0]], [[3dn1]], [[3dn2]], [[3dn3]], [[3dn4]], [[3dn6]], [[3dn8]], [[3dna]], [[2rb1]], [[2ray]], [[2raz]], [[2rb0]], [[2rb2]], [[2rbn]], [[2rbo]], [[2rbq]], [[2rbr]], [[2rbs]], [[2oty]],[[2otz]], [[1owy]], [[1owz]], [[1ov5]], [[1ov7]], [[1ovh]], [[1ovj]], [[1ovk]], [[1lgw]], [[1lgx]], [[1li2]], [[1li3]], [[1l83]], [[1l84]] – T4Lys (mutant) + benzene derivative 
[[3htd]], [[3htf]], [[3htg]], [[3hu9]], [[3hua]], [[3huk]], [[3hh3]], [[3hh4]], [[3hh5]], [[3hh6]], [[2rbp]], [[2ou0]], [[2f2q]], [[2f32]], [[2f47]], [[1xep]] – T4Lys (mutant) + inhibitor 
[[148l]] - T4Lys (mutant) + glucoside 
[[3d3d]], [[1d9u]] – lamLys + chitohexasaccharide 
[[1am7]] – lamLys - Enterobacteria phage λ 
[[2anv]], [[2anx]] – Lys (mutant)]] - Enterobacteria phage p22 
[[1xjt]], [[1xju]] - Lys - Enterobacteria phage p1 
[[1lba]] - T7Lys - Enterobacteria phage T7 

===Lys protein complex===

[[3m18]], [[3g3a]], [[3g3b]] - HEWL + Variable lymphocyte receptor – Marine lamprey 
[[3a67]], [[3a6b]], [[3a6c]], [[2yss]], [[2eiz]], [[2dqc]], [[2dqd]], [[2dqe]], [[2dqf]], [[2dqg]], [[2dqh]], [[2dqi]], [[2dqj]], [[1j1o]], [[1j1p]], [[1j1x]], [[1ic4]], [[1ic5]], [[1ic7]] – HEWL + mLys antibody HYHEL-10 (mutant) 
[[1xgp]], [[1xgq]], [[1xgr]], [[1xgt]], [[1xgu]] – HEWL + mLys antibody HYHEL-63 
[[3d9a]], [[2eks]], [[1ua6]], [[1c08]], [[3hfm]] – HEWL + mLys antibody HYHEL-10 
[[1uac]] - tuLys C + mLys antibody HYHEL-10 
[[1yqv]], [[2iff]] – HEWL + mLys antibody HYHEL-5 
[[1bql]] – BqLys + mLys antibody HYHEL-5 
[[1ndg]] – HEWL + mLys antibody HYHEL-8 
[[1ndm]] – HEWL + mLys antibody HYHEL-26 
[[1dqj]] - HEWL + mLys antibody HYHEL-63 
[[1nby]], [[1nbz]] – HEWL (mutant) + mLys antibody HYHEL-63 
[[1g7h]], [[1g7i]], [[1g7j]], [[1g7l]], [[1g7m]], [[1kip]], [[1kiq]], [[1kir]] – HEWL + mAnti-HEWL monoclonal antibody (mutant) 
[[1mlc]], [[1vfb]] - HEWL + mIGG1-κ D44.1 FAB 
[[1a2y]] - HEWL (mutant) + mIGG1-κ D1.3 FV 
[[1fdl]] - HEWL + mIGG1-κ D1.3 FAB 
[[1jhl]] – phLys + mIGG1-κ D11.15 FV 
[[1fbi]] – GfLys + mIGG1 F9.13.7 FAB 
[[2znw]], [[2znx]] – HEWL + hSCFV10 antibody 
[[1bvk]] - HEWL + hAnti Lys FV antibody 
[[1dzb]] – tuLys + mSCFV 1F9 
[[1zv5]], [[1zvh]], [[1zvy]], [[1zmy]], [[1ri8]], [[1rjc]], [[1xfp]], [[1jtp]], [[1jtt]], [[1jto]], [[1mel]] - HEWL + cAntibody heavy chain domain – camel 
[[1op9]] - hLys C + cAntibody heavy chain domain 
[[3otp]] – HEWL + EcProtease DO – ''Escherichia coli'' 
[[3f6z]] - HEWL + MLIC – ''Pseudomonas aeruginosa'' 
[[3eba]] – hLys C + hCABHUL6 
[[2qb0]], [[2qar]] – T4Lys/E80 TELSAM domain 
[[2i25]], [[2i26]] - HEWL +NsAntigen receptor PBLA8 variable domain – Nurse shark 
[[1sq2]], [[1t6v]] – HEWL +NsNew Antigen receptor variable domain 
[[1gpq]] – HEWL + EcInhibitor of Vertebrate Lys 
[[1aro]] – T7Lys + T7 RNA polymerase 

===Some Useful External Links===
[http://en.wikipedia.org/wiki/Lysozyme Lysozyme]

[http://en.wikipedia.org/wiki/Glycoside_hydrolase#Retaining_glycoside_hydrolases Retaining Glycoside Hydrolases]

===References===
<references/>

Hen Egg-White (HEW) Lysozyme

2011-04-20T17:58:10Z

Anne Goodling:

'''Introduction'''

Lysozyme - also known as muramidase, or glycoside hydrolase - is a powerful enzyme of biological significance found in abundance in tears, saliva, and human milk. In humans, it is encoded in the ''LYZ'' gene. Although it is responsible for the initial digestion of starches in the mouth, it is most widely identified as a non-specific defense in gram positive bacteria and in many species of fungi. Due to its antibacterial effects, it is a strong component of the innate immune system, and is an important part of an infant's diet to ward off diarrheal diseases. Since it is a small, easily available, and highly stable protein containing only 129 amino acid residues, it has been subject to extensive research regarding its function and structure. Hen Egg White (HEW) Lysozyme is shown below.

===History===

Lysozyme is an enzyme known for its unique ability to degrade the polysaccharide architecture of many kinds of cell walls, normally for the purpose of protection against bacterial infection<ref>Lysozyme. 2010. Citizendium.org. http://en.citizendium.org/wiki/Lysozyme</ref>. Its effects were first noticed by Laschtschenko in 1909. It was officially characterized and termed “lysozyme” by Alexander Fleming, the same person credited for the accidental discovery of penicillin.
The characterization of lysozyme in 1922 by Alexander Fleming was providential in that the undertaken experiment related to the discovery of lysozyme was not geared toward any knowledge of such a protein as lysozyme <ref>Lysozyme. 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>. During the unrelated experiment, nasal drippings were inadvertently introduced to a petri dish containing a bacterial culture, which culture consequently exhibited the results of an as yet unknown enzymatic reaction. The observation of this unknown reaction led to further research on the components of this reaction as well as to the corresponding identification of the newfound "lysozyme." Fleming's discovery was complemented by David C. Phillips' 1965 description of the three-dimensional structure of lysozyme via a 200 pm resolution model obtained from X-ray crystallography <ref>Lysozyme, 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>. Phillips' work was especially groundbreaking since Phillips had managed to successfully elucidate the structure of an enzyme via X-ray crystallography - a feat that had never before been accomplished<ref>Bugg, T. 1997. An Introduction to Enzyme and Coenzyme Chemistry. Blackwell Science Ltd., Oxford </ref>. Phillips' research also led to the first sufficiently described enzymatic mechanism of catalytic action <ref>1967. Proc R Soc Lond B Bio 167 (1009): 389–401.</ref>. Thus, Phillips' elucidation of the function of lysozyme led Phillips to reach a more general conclusion on the diversity of enzymatic chemical action in relation to enzymatic structure. Clearly, the findings of Phillips as well as the more general historical development of the understanding of the structure and function of lysozyme have been paramount to the more general realm of enzyme chemistry.

[[Image:nag-nam2.jpg|thumb|left|350px|Lysozyme Cleavage Site]]
<ref>Image from: http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/proteins/lysozyme.htm</ref>

'''Function'''

Lysozyme is known for damaging bacterial cell walls by catalyzing the hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid (NAM) and N-acetyl-D-glucosamine (NAG) residues in peptidoglycan, and between N-acetyl-D-glucosamine residues in chitodextrins. In this way, lysozyme is efficient in lysing the cell walls of both bacteria and fungi. The location of cleavage for lysozyme on this architectural theme is the β(1-4) glycosidic linkage connecting the C1 carbon of NAM to the C4 carbon of NAG.

The particular substrate of preference for this cleavage type is a (NAG-NAM)₃ hexasaccharide, within which substrate occurs the
cleaving target glycosidic bond, NAM₄-β-O-NAG₅. The individual hexasaccharide binding units are designated A-F, with NAM₄-β-O-NAG₅ glycosidic bond cleavage preference corresponding to a D-E unit glycosidic bond cleavage preference.

= Enzymatic Activity of Lysozyme =

Enzymes are designed to attract and to bind specific substrates. The active site of and lysozyme and its specific ligands are described in the following sections

==Mechanistic Features==

'''Zymogen of Lysozyme: Enzymatic Precursor'''

Zymogens are inactive enzyme precursors. Enzymes are developed in an inactive way to prevent the enzyme from digesting the cell that produced it. This process also prevents the enzyme from becoming active in the wrong portion of the body. Lysozyme's zymogen, simply titled “pre-lysozyme,” was sequenced in 1977 by R D Palmiter, J Gagnon, L H Ericsson and K A Walsh, and has since been sequenced much more extensively.

[[Image:jrip.jpg|thumb|left|350px|Mechanism of Lysozyme]]
<ref>Image from: http://www.google.com/imgres?imgurl=http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/pics-and-strucs/lysozyme-mech.gif&imgrefurl=http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/proteins/lysozyme.htm&usg=__ormapG4XKg-tR5GrMSOdSMTV4vE=&h=603&w=801&sz=7&hl=en&start=17&zoom=1&tbnid=nvr9gvFrUILDkM:&tbnh=143&tbnw=189&prev=/images%3Fq%3DThe%2Blysozyme%2Breaction%2Bmechanism%26um%3D1%26hl%3Den%26sa%3DN%26biw%3D1280%26bih%3D647%26tbs%3Disch:10%2C304&um=1&itbs=1&iact=hc&vpx=521&vpy=349&dur=448&hovh=191&hovw=254&tx=140&ty=48&ei=JQ_LTPKzLIjCsAPkzt2KDg&oei=IA_LTP74OsG78gapm-GFAQ&esq=2&page=2&ndsp=18&ved=1t:429,r:2,s:17&biw=1280&bih=647</ref>

'''Mechanism'''

The lysozyme mechanism of action results in the hydrolysis of a glycoside (hence the familial distinction of lysozyme as a glycosylase<ref>Lysozyme, 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>), which corresponds to the conversion of an acetal to a hemiacetal, which reaction (general degradation of glycosidic bond to units "capped" by newly formed hydroxyl groups) necessitates acid catalysis, since the conversion of acetal to hemiacetal involves the protonation of the reactant oxygen prior to actual bond cleavage. <ref>Pratt, C.W., Voet, D., Voet, J.G. Fundamentals of Biochemistry - Life at the Molecular Level - Third Edition. Voet, Voet and Pratt, 2008.</ref>. Furthermore, the transition state obtained from this protonation is a covalent, oxonium ion, intermediate that must obtain resonance stabilization. The need for some means of acid catalysis and covalent resonance stabilization is adequately provided by the Glu 35 and Asp 52 residues of lysozyme, respectively. The reaction mechanism of lysozyme is demonstrated below. In the following image, the reaction begins at the upper left-hand side, and proceeds according to reaction arrows.

As seen to the left, lysozyme works by hydrolyzing the glycosidic bond, distorting the bond between the NAM and NAG. This produces a glycosyl enzyme intermediate, which reacts with a water molecule to produce the product and the unchanged enzyme.

'''Active Site'''

The <scene name='Hen_Egg-White_(HEW)_Lysozyme/Act_site/2'>active site</scene> of lysozyme is formulated as a prominent cleft outlined by the two aforementioned catalytic amino acids, Glu 35 (green) and Asp 52 (red). The active site is geometrically bent to augment ligand binding, and the two amino acids interact with the ligand in the binding site. Asp52 is depicted in green, and Glu35 is depicted in purple.

<applet load='1hew' size='350' frame='true' align='right' caption='' />

==Binding==
'''Ligands'''

A <scene name='Sandbox_39/Ligands_1/1'>ligand</scene> is able to bind to the active site of an enzyme to form a biologically relevant complex. The model to the right shows a space-filling model of lysozyme with the protein distinguishable in brown and the ligand distinguishable in green. Another model of the ligand can be seen in this
<scene name='Sandbox_39/Ribbon_ligand/1'>ribbon diagram</scene>, with the ligand protruding as a space-filling model from the active site. Here, it is clear that the ligand is a polysaccharide.

The lysozyme reaction is characterized by hydrolysis of the beta (1-4) glycosidic bond between NAM and NAG. Lysozyme has a very specific active site, which can bind only six sugar rings from a polysaccharide chain. Once lysozyme binds to this chain, it hydrolyzes them. These six sugar rings represent the ligand of lysozyme. The lysozyme then distorts the fourth sugar in the six-membered complex, producing stress on the molecule and breaking the glycosidic bond.

The amino acid side-chains Glu35 and Asp52 are critical to the activity of this enzyme. Glu35 acts as a proton donor to the glycosidic bond, cleaving the C-O bond in the substrate, and Asp52 acts as a nucleophile to generate a glycosyl enzyme intermediate. The glycosyl enzyme intermediate then reacts with a water molecule to give the product of hydrolysis.

'''Inhibitors'''

Lysozyme is best inhibited by small saccharides which act competitively with the natural substrate. The smaller saccharides will bind to the first three binding sites of the cleft (sites A-C), but will not reach sites D and E, where the enzyme cuts the glycosidic bond. So, the competitive inhibitor will stick in the cleft, not allowing the substrate to bind to the enzyme complex.<ref>http://mcdb-webarchive.mcdb.ucsb.edu/sears/biochemistry/tw-enz/lysozyme/HEWL/lysozyme-overview.htm</ref> Several known inhibitors of lysozyme are: SDS, N-acetyl-D-glucosamine, and various alcohols and oxidizing agents.<ref>http://www.worthington-biochem.com/ly/default.html</ref>

<applet load='1hew' size='350' frame='true' align='left' caption='' />

= Composition and Structure of Lysozyme =

All proteins consist of carbon, hydrogen, nitrogen, oxygen, and sulfur, as do most organic molecules. Enzymes are composed in such a way as to maximize their reactivity with their desired substrate, increasing the efficiency of biological reactions. The <scene name='Sandbox_39/Elements/1'>composition of lysozyme</scene> can be seen on the left, with the carbon atoms outlined in gray, oxygen atoms in red, nitrogen atoms in blue, sulfur atoms in yellow, and the three-letter abbreviation for the <scene name='Sandbox_39/Amino_acid_residues/1'>amino acid residues</scene> in purple.

Lysozyme, like all proteins, also contains a <scene name='Sandbox_39/C_and_n_terminal_residues/1'> 3'C and 5'N terminal </scene>, and these can be seen by following the colors of the rainbow across the molecule. Starting at the red end, the 3' C terminal end, one can work the entire way through to the 5' N terminal end, showing the folding pattern and chain of the protein.

== Secondary Structure ==

Lysozyme contains five <scene name='Sandbox_38/A/2'>alpha helical</scene> regions and five regions containing <scene name='Sandbox_38/B/1'>beta sheets</scene> as displayed in this <scene name='Sandbox_38/Alphab/1'>image</scene>. Linking these secondary structures, a number of beta turns and a large number of random coils make up the remainder of the polypeptide backbone. The polypeptide backbone of lysozyme involved in the 3 antiparallel beta sheets display the beta hairpin motif of supersecondary structure. This depiction of lysozyme contains an antiparallel beta-pleated sheet, which contributes greatly to the stability of the molecule by providing the correct alignment of hydrogen bonds. Lysozyme also contains a great deal of random coil, which is seen in the white regions of the molecule.

==Amino Acid Residues==

The amino acids present in the lysozyme polypeptide sequence have a direct influence not only on primary structure, but also on the secondary and tertiary structures, which can be influenced by polarity and charge of the sidechains. The various amino acid <scene name='Sandbox_38/Aminoi/1'>residues</scene> differ in their properties because of the great variety of side chains present on each amino acid. Polar and nonpolar (and charged and uncharged) side chains lead to various degrees of hydrophobicity and hydrophilicity, which affects protein folding. In lysozyme, these <scene name='Sandbox_38/Sc/1'>side chains</scene> are displayed for each amino acid residue.

= Bonding Interactions =

'''Disulfide Bonding in Lysozyme'''

Lysozyme contains four <scene name='Sandbox_39/Disulfide_bonds/1'>disulfide bonds</scene> involving eight cysteine residues, which are highlighted in yellow on the left. Disulfide bonds are intramolecular forces that stabilize the tertiary structure of many proteins. Disulfide bonds are present in four locations in lysozyme: between Cys 6 and Cys 127, between Cys 30 and Cys 115, between Cys 64 and Cys 80 and between Cys 76 and Cys 94.

'''Hydrogen Bonding'''

In all proteins <scene name='Sandbox_39/Hydrogen_bonds/2'>hydrogen bonds</scene> are essential for stability. In this ribbon diagram, the hydrogen bonds can be seen between the secondary structures of lysozyme highlighted in orange. Since the double bonds of the alpha carbons in the main chain of lysozyme cause torsional strain, lysozyme is limited to very specific hydrogen bonding between the amino acid residues. This representation clearly shows how crucial hydrogen bonding is to help maintain the stability of the protein.

<applet load='1hew' size='350' frame='true' align='left' caption='' />

= Intermolecular Interactions =

'''Hydrophobicity'''

Lysozyme contains both hydrophobic and hydrophilic regions ( <scene name='Sandbox_39/Hydrophobicity/2'>Hydrophobicity</scene> ). The hydrophilic effect, or the desire for proteins to be at a specific position regarding water, is the single most important determinant of protein folding. These regions can be displayed with the hydrophobic regions in gray and the polar, hydrophillic regions in purple. This coloration highlights the location of these regions, showing that the majority of the hydrophobic regions are inside of the protein and that the majority of the hydrophillic regions are on the outside of the protein.

'''Polarity'''

The nature of the amino acid sidechains in the lysozyme polypeptide sequence leads to regions of varying hydrophobicities and polarities of the enzyme structure. The presence of certain regions of hydrophilicity and hydrophobicity is a driving force in determining protein structure when folding. The varying polarities of the side chains influence the locations of residues in the enzyme structure. Nonpolar residues appear blue, and polar residues appear red in the following <scene name='Sandbox_38/Non_polar_blue/1'>polarity</scene> display of lysozyme. Nonpolar residues will display hydrophobic tendencies occurring mostly on the interior of the enzyme while polar residues will increase in abundance on the surface of the protein in order to increase contact with the aqueous solvent so as to satisfy their hydrophilic nature. By observing a space-filled structural depiction of <scene name='Sandbox_38/Non_polar_blu/1'>lysozyme polarity</scene> with polar molecules colored red and nonpolar molecules colored blue the influence of polarity on nucleotide arrangement and protein folding is evident, with the blue (nonpolar) regions inside the red (polar) regions. The presence of <scene name='Sandbox_39/Water/1'>water</scene> interacting with the various hydrophilic residues is depicted to further display how polarity affects structure. Water is depicted as yellow, and the polar and nonpolar regions remain their respective color.

'''Charge'''

Charges of the various regions of the lysozyme structure display a hydrophilic nature and thus also affect the location of that region of polypeptides and the overall folding of the protein. Charged regions of the protein will display hydrophilic tendencies and therefore will most often be located on the surface of the lysozyme molecule where they can interact with the aqueous solvent. Non-charged portions will display hydrophobic tendencies and be located on the interior of the molecule. The effect of various <scene name='Sandbox_38/Rb/1'>charges</scene> on protein structure can be visualized with charged molecules represented by red anionic and blue cationic regions, and uncharged regions colored in grey. This depiction of lysozyme uses a spacefill representation of lysozyme to depict <scene name='Sandbox_38/Chargeddd/1'>charges</scene>.

= Applications of Lysozyme =

Since lysozyme has been widely recognized for its antibacterial and antifungal properties, it has a wide variety of uses both in biochemical and pharmaceutical applications. In molecular biology, lysozyme is often used in the alkaline-lysis procedure for extracting and isolating plasmid DNA. It is used extensively in the pharmaceutical field for destroying gram-positive bacteria, and can be used to support already-existing immune defenses to fight bacterial infections. This enzyme is particularly important for preventing bacterial diseases in infants. Because of its antibacterial properties, lysozyme can also be used in the food industry to help prevent spoilage of foods.

= Discovery and Applications of Hen Egg-White Lysozyme=

<applet load='aln_1H6M_to_1HEW_2.pdb' size='300' frame='true' align='right' caption=' Hen Egg White (HEW) Lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to the active site, PDBid 1HEW' scene='User:Judy_Voet/Lysozyme/Lysozyme1/16' />
Lysozyme was the first enzyme whose X-ray structure was determined <ref> PMID 5840126</ref><ref>Phillips, D. C. The hen egg white lysozyme molecule. Proc. Natl Acad. Sci. USA 57, 483-495 (1967)</ref>. This <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>scene </scene> shows Hen Egg White (HEW) lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to a cleft in the enzyme. David Phillips, who determined the structure in 1965, saw that the cleft was large enough to fit three more saccharide units.
He therefore built a model extending the trisaccharide to a
<scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> that fits into the cleft, labeling the sugar subsites A-F<ref> coordinates of the model kindly provided by Louise Johnson</ref>. Alternately click on <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>trisaccharide</scene> and <scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> to turn the modeled portion of the hexasaccharide on and off.

The interesting thing about the model was that the only way that the hexasaccharide would fit into the cleft was if the 4th saccharide (in subsite D) was strained into a <scene name='User:Judy_Voet/Lysozyme/Half-chair/2'>half-chair conformation</scene>. This conformation is what would be necessary for the formation of an oxocarbenium ion (oxionium ion). When the model was studied, <scene name='User:Judy_Voet/Lysozyme/Glu_35/1'>Glu 35</scene> was found to be in an ideal location to act as a general acid catalyst, 3.34 Angstroms from the bridging oxygen between the 4th and 5th saccharide units. <scene name='User:Judy_Voet/Lysozyme/Asp_52/2'>Asp 52</scene> appeared to be too far away (2.69 angstroms) in the static lysozyme structure to have formed a covalent bond with C1 of the half-chair model in the D site, and no covalent intermediate had ever been detected, so Phillips proposed that it acted as an electrostatic stabilizer of the oxonium ion (referred to as The Phillips Mechanism).

<applet load='aln_1H6M_to_1HEW_2.pdb' size='200' frame='true' align='left' caption='NAG-2-deoxy-2-fluoro-glucosyl fluoride (NAG2FGlcF) bound to Glu35Gln HEW Lysozyme PDBid 1H6M' scene='User:Judy_Voet/Lysozyme/1h6m/3'/>

Then, in 2001, Stephen Withers published <scene name='User:Judy_Voet/Lysozyme/1h6m/3'>1H6M</scene>,<ref>PMID 11518970</ref> in which Glu 35 had been mutated to Gln to remove the general acid catalyst. The substrate contained NAG-2-fluoro-glucosyl fluoride (NAG2FGlcF). The fluoro group on C-1 does not require acid catalysis to be a good leaving group, and the remaining saccharide, in the absence of the acid necessary to catalyse the second step of the reaction, was demonstrated to form a <scene name='User:Judy_Voet/Lysozyme/Covalent/1'> covalent intermediate</scene>. In this <scene name='User:Judy_Voet/Lysozyme/Superposition/2'>superposition</scene> of the half chair model with 1HEW (greens) and the covalent intermediate in 1H6M (blues), note the relatively small motions of Asp 52 and C1 of the sugar ring in going from the model to the covalent intermediate. to observe the motion from the <scene name='User:Judy_Voet/Lysozyme/Asp52_halfchair/1'>half-chair</scene> to the <scene name='User:Judy_Voet/Lysozyme/Covalent/2'>covalent intermediate</scene> just toggle between the two green links.

== 3D Structures of Lysozyme ==

===Lys===

[[2x0a]], [[3iju]], [[3ijv]], [[3a8z]], [[2w1y]], [[2w1m]], [[2w1x]], [[2w1l]], [[3e3d]], [[3exd]], [[2zq3]], [[2zq4]], [[3b72]], [[3b6l]], [[2z12]], [[2z18]], [[2z19]], [[2vb1]], [[2hu3]], [[2hub]], [[2htx]], [[2hu1]], [[2yvb]], [[2epe]], [[2g4p]], [[2g4q]], [[2cgi]], [[2b5z]], [[2d4k]], [[2d91]], [[2f2n]], [[2fbb]], [[2c8o]], [[2c8p]], [[2a6u]], [[2aub]], [[2blx]], [[2bly]], [[2a7d]], [[2a7f]], [[1wtm]], [[1wtn]], [[1w6z]], [[1vdp]], [[1vdq]], [[1vds]], [[1vdt]], [[1ved]], [[1v7t]], [[1ps5]], [[2cds]], [[1lj3]], [[1lj4]], [[1lje]], [[1ljf]], [[1ljg]], [[1ljh]], [[1lji]], [[1ljj]], [[1ljk]], [[1jis]], [[1jit]], [[1jiy]], [[1jj0]], [[1jj1]], [[1jj3]], [[1iee]], [[1qio]], [[1f0w]], [[1f10]], [[1dpx]], [[1c10]], [[1qtk]], [[1lz8]], [[1lz9]], [[1bhz]], [[1bgi]], [[1bwh]], [[1bwi]], [[1bwj]], [[1bvx]], [[1hsw]], [[1hsx]], [[1lpi]], [[4lzt]], [[3lzt]], [[1aki]], [[1jpo]], [[1rfp]], [[193l]], [[194l]], [[5lym]], [[1lza]], [[3lyt]], [[4lyt]], [[5lyt]], [[6lyt]], [[2lzt]], [[1lzt]], [[1lzh]], [[2lzh]], [[7lyz]], [[1lyz]], [[2lyz]], [[3lyz]], [[4lyz]], [[5lyz]], [[6lyz]] - HEWL – chicken 
[[1xei]], [[1xej]], [[1xek]], [[1uco]], [[1lma]], [[4lym]] – HEWL low hydration 
[[1lsa]], [[1lsb]], [[1lsc]], [[1lsd]], [[1lse]], [[1lsf]], [[1lys]] – HEWL temperature influence 
[[2lym]], [[3lym]] – HEWL pressure influence 
[[132l]] – HEWL methylated 
[[1rcm]] – HEWL 3 S-S form 
[[2xbr]], [[2xbs]]- HEWL– Raman crystallography 
[[2zwb]], [[1io5]], [[1lzn]] - HEWL– Neutron 
[[1gxv]], [[1gxx]], [[1e8l]] - HEWL- NMR 
[[2hs7]], [[2hso]], [[2hs9]]- HEWL– Powder diffraction 
[[1ir7]], [[1ir8]], [[1ir9]], [[1ioq]], [[1ior]], [[1ios]], [[1iot]], [[1flq]], [[1flu]], [[1flw]], [[1fly]], [[1fn5]], [[1kxw]], [[1kxx]], [[1kxy]], [[1uia]], [[1uib]], [[1uic]], [[1uid]], [[1uie]], [[1uif]], [[1uig]], [[1uih]], [[1lsm]], [[1lsn]], [[1hel]], [[1hem]], [[1hen]], [[1heo]], [[1hep]], [[1heq]], [[1her]] – HEWL (mutant) 
[[1lyo]], [[2lyo]], [[3lyo]], [[4lyo]] – HEWL cross-linked 
[[1xft]] - tuLys – turkey - Powder diffraction 
[[1jse]], [[1tew]], [[135l]], [[2lz2]], [[1lz2]] – tuLys 
[[3lz2]] – tuLys - Laue 
[[3ab6]] – Lys + NAG3 – Hard clam 
[[2x8r]] – Lys GH25 – ''Aspergillus fumigatus'' 
[[3mgw]] – Lys G – Atlantic salmon 
[[3gxk]], [[3gxr]] – Lys G + NAG – Atlantic cod 
[[2fbd]] – HfLys 1 
[[3cb7]] – HfLys 2 
[[2zij]], [[2zik]], [[2zil]], [[2nwd]], [[1iwt]], [[1iwu]], [[1iwv]], [[1iww]], [[1iwx]], [[1iwy]], [[1iwz]], [[1jwr]], [[1jsf]], [[1rex]], [[1lz1]] – hLys – human 
[[1w08]], [[1ix0]], [[1ioc]], [[1ip1]], [[1ip2]], [[1ip3]], [[1ip4]], [[1ip5]], [[1ip6]], [[1ip7]], [[1qsw]], [[1gev]], [[1gez]], [[1gf0]], [[1gf3]], [[1gf4]], [[1gf5]], [[1gf6]], [[1gf7]], [[1i1z]], [[1i20]], [[1i22]], [[1gfr]], [[1gft]], [[1gfu]], [[1gfv]], [[1gf8]], [[1gf9]], [[1gfa]], [[1gfe]], [[1gfg]], [[1gfh]], [[1gfj]], [[1gfk]], [[1inu]], [[1gdx]], [[1ge0]], [[1ge1]], [[1ge2]], [[1ge3]], [[1ge4]], [[1gdw]], [[1gaz]], [[1gb0]], [[1gb2]], [[1gb3]], [[1gb5]], [[1gb6]], [[1gb7]], [[1gb8]], [[1gb9]], [[1gbo]], [[1gbw]], [[1gbx]], [[1gby]], [[1gbz]], [[1gay]], [[1eq4]], [[1eq5]], [[1eqe]], [[1c7p]], [[1di3]], [[1di4]], [[1di5]], [[1c43]], [[1c45]], [[1c46]], [[1ckg]], [[1cj6]], [[1cj7]], [[1cj8]], [[1cj9]], [[1ckc]], [[1ckd]], [[1ckf]], [[1ckh]], [[1b5z]], [[1b70]], [[1b7q]], [[1b7r]], [[1b7s]], [[1b7l]], [[1b7m]], [[1b7n]], [[1b7p]], [[1b5u]], [[1b5v]], [[1b5w]], [[1b5x]], [[1b5y]], [[1bb3]], [[1bb4]], [[2bqa]], [[2bqb]], [[2bqc]], [[2bqd]], [[2bqe]], [[2bqf]], [[2bqg]], [[2bqh]], [[2bqi]], [[2bqj]], [[2bqk]], [[2bql]], [[2bqm]], [[2bqn]], [[2bqo]], [[2mea]], [[2meb]], [[2mec]], [[2med]], [[2mee]], [[2mef]], [[2meg]], [[2meh]], [[2mei]], [[1wqm]], [[1wqn]], [[1wqo]], [[1wqp]], [[1wqq]], [[1wqr]], [[2heb]], [[2hea]], [[2hec]], [[2hed]], [[2hee]], [[2hef]], [[1jka]], [[1jkb]], [[1jkc]], [[1jkd]], [[1loz]], [[1lyy]], [[1oua]], [[1oub]], [[1ouc]], [[1oud]], [[1oue]], [[1ouf]], [[1oug]], [[1ouh]], [[1oui]], [[1ouj]], [[207l]], [[208l ]], [[1yam]], [[1yan]], [[1yao]], [[1yap]], [[1yaq]], [[1lmt]], [[1lhh]], [[1lhi]], [[1lhj]], [[1lhk]], [[1lhl]], [[133l]], [[134l]], [[1lz4]], [[1lz5]], [[1lz6]], [[1laa]], [[1tay]], [[1tby]], [[1tcy]], [[1tdy]], [[2lhm]], [[3lhm]] – hLys (mutant) 
[[1iy3]], [[1iy4]] – hLys - NMR 
[[2z2f]] – Lys – Bovine 
[[2cwi]], [[1el1]], [[1qqy]] – dLys - dog 
[[2z2e]] – dLys (mutant) 
[[1i56]] – dLys – NMR 
[[2dqa]] – Lys – ''Tapes japonica'' 
[[2gv0]] – Lys – Soft-shelled turtle 
[[1ivm]] – mLys M – NMR – mouse 
[[1jfx]] – Lys – ''Streptomyces coelicolor'' 
[[1gd6]] – Lys – ''Bombyx mori'' 
[[1jug]] – Lys – Echidna 
[[1dkj]] – BqLys – Bobwhite quail 
[[2ihl]] – Lys – Japanese quail 
[[1gbs]] – BsLys – Black swan 
[[1lmn]] – RtLys – Rainbow trout 
[[2eql]] – Lys – horse 
[[1ghl]] – phLys – pheasant 
[[1hhl]] – GfLys – Guinea fowl 
[[1lhm]] – Lys (mutant) – yeast 

===Lys small molecules complexes===

[[3fe0]], [[2d4i]], [[2d4j]], [[1v7s]] - HEWL+ D2O 
[[3m3u]] – HEWL Trp fluorescence 
[[2xjw]] - HEWL + CO 
[[1hf4]], [[1lks]] – HEWL + NO3 
[[3a34]], [[3ems]] - HEWL + arginine 
[[2xth]] – cLys + inhibitor K2PtBr6 
[[3a90]], [[3a91]], [[3a92]], [[3a93]], [[3a94]], [[3a95]], [[3a96]], [[3kam]], [[2pc2]], [[2bpu]], [[1t3p]], [[1h87]] – HEWL + rare earth 
[[2d6b]], [[2hg0]], [[1vat]], [[1gwd]], [[1b2k]], [[1lkr]], [[1azf]], [[8lyz]]- HEWL+ halogen 
[[1vat]] - HEWL + Xe 
[[1n4f]] - HEWL + As 
[[2i6z]] - HEWL + Pt drug 
[[2zyp]] - HEWL + poly (allyl amine) 
[[2f30]], [[2f4a]] – HEWL + urea derivative 
[[2f4g]], [[1ykx]], [[1yky]], [[1ykz]], [[1yl0]], [[1yl1]], [[1z55]] - HEWL + alcohol 
[[1dpw]] – HEWL + MPD 
[[1lcn]] – HEWL + SCN 
[[2zxs]] - HEWL with glycine-amide 
[[2h9j]], [[2h9k]], [[1yik]], [[1yil]] - HEWL + cyclam derivative 
[[1b0d]] – HEWL + p-toluene-sulfonate 
[[2q0m]] - HEWL + tricarbonylmanganese 
[[2war]] – HEWL (mutant) + chitopentaose 
[[2h5z]] – HfLys 1 + chitotetraose – House fly 
[[1hnl]] – hLys + glutathione 
[[1dkk]] – BqLys + NO3 

===Lys complex with glucoside===

[[3a3q]] – HEWL (mutant) + NAG 
[[1sf4]], [[1sf6]], [[1sf7]], [[1sfb]], [[1sfg]], [[1ja2]], [[1ja4]], [[1ja6]], [[1ja7]] – HEWL + NAG oligosaccharide – Powder diffraction 
[[1ubz]], [[1d6p]], [[1d6q]], [[1bb5]] – hLys (mutant) + glycoside 
[[1uc0]], [[1re2]], [[1rem]], [[1rey]], [[1rez]], [[1lzr]], [[1lzs]] - hLys + glycoside 
[[1ljn]], [[1jef]], [[1lzy]] – tuLys + glycoside 
[[1h6m]], [[1at5]], [[1at6]], [[1lzb]], [[1lzc]], [[1lzd]], [[1lze]], [[1lzg]], [[1hew ]]– HEWL + glycoside 
[[1lsy]], [[1lsz]] - HEWL (mutant) + glycoside 
[[1bb6]], [[1bb7]] – RtLys + glycoside 
[[1lmc]] – RtLys + bulgecin 
[[1lmo]], [[1lmp]], [[1lmq]] – RtLys + glucoside 
[[1lsp]] – BsLys + bulgecin 
[[153l]], [[154l]] – Lys +glucoside – goose 

===Phage Lys===

[[2oe4]], [[2oe7]], [[2oe9]], [[2oea]], [[1swz]], [[1cx6]], [[1qtc]], [[1qtd]], [[1qth]], [[1qsb]], [[1qs5]], [[1qs9]], [[1qtb]], [[256l]], [[206l]], [[167l]], [[168l]], [[169l]], [[170l]], [[171l]], [[172l]], [[173l]], [[174l]], [[175l]], [[176l]], [[177l]], [[178l]], [[181l]], [[182l]], [[183l]], [[184l]], [[185l]], [[186l]], [[187l]], [[188l]], [[1nhb]], [[137l]], [[216l]], [[152l]], [[149l]], [[150l]], [[151l]], [[1lyd]], [[2lzm]] - T4Lys – Enterobacteria phage T4 
[[138l]] – T4Lys cross-linked 
[[4lzm]], [[5lzm]], [[6lzm]], [[7lzm]] – T4Lys ionic strength 
[[3l2x]], [[3k2r]], [[3g3v]], [[3g3w]], [[3g3x]], [[2q9d]], [[2q9e]], [[2igc]], [[2ntg]], [[2nth]], [[2ou8]], [[2ou9]], [[1zur]], [[1zwn]], [[1zyt]], [[2cuu]], [[2a4t]] – T4Lys (mutant) spin labeled 
[[3l64]], [[3hwl]], [[3jr6]], [[3gui]], [[3c7w]], [[3c7y]], [[3c7z]], [[3c80]], [[3c81]], [[3c82]], [[3c83]], [[3c8q]], [[3c8r]], [[3c8s]], [[3cdo]], [[3cdq]], [[3cdr]], [[3cdt]], [[3cdv]], [[3f8v]], [[3f9l]], [[3fa0]], [[3fad]], [[3fi5]], [[3dke]], [[3dmv]], [[2o4w]], [[2o79]], [[2o7a]], [[2huk]], [[2hul]], [[2hum]], [[2b7x]], [[2b6t]], [[2b6w]], [[2b6x]], [[2b6y]], [[2b6z]], [[2b70]], [[2b72]], [[2b73]], [[2b74]], [[2b75]], [[1sx7]], [[1swy]], [[1sx2]], [[1t6h]], [[1ssw]], [[1ssy]], [[1t8f]], [[1t8g]], [[1t8a]], [[1t97]], [[1p56]], [[1p5c]], [[1p2l]], [[1p2r]], [[1p36]], [[1p37]], [[1p3n]], [[1p46]], [[1p64]], [[1p6y]], [[1p7s]], [[1pqd]], [[1pqi]], [[1pqj]], [[1pqk]], [[1pqm]], [[1pqo]], [[1oyu]], [[1ks3]], [[1kw5]], [[1kw7]], [[1ky0]], [[1ky1]], [[1l0j]], [[1l0k]], [[1lw9]], [[1lwg]], [[1lwk]], [[1lpy]], [[1llh]], [[1lgu]], [[1li6]], [[1jtm]], [[1jtn]], [[1jqu]], [[1kni]], [[1g06]], [[1g07]], [[1g0g]], [[1g0j]], [[1g0k]], [[1g0l]], [[1g0m]], [[1g0p]], [[1g0q]], [[1g1v]], [[1g1w]], [[1i6s]], [[257l]], [[258l]], [[260l]], [[1epy]], [[1b6i]], [[1cu6]], [[1d9w]], [[1ctw]], [[1cu0]], [[1cu2]], [[1cu3]], [[1cu5]], [[1cv1]], [[1cv4]], [[1cv5]], [[1cv6]], [[1cvk]], [[1cx7]], [[1d2w]], [[1d2y]], [[1d3f]], [[1d3j]], [[1d3m]], [[1d3n]], [[1cv3]], [[1qt3]], [[1qt4]], [[1qt5]], [[1qt6]], [[1qt7]], [[1qt8]], [[1qtv]], [[1qtz]], [[1qud]], [[1qug]], [[1quh]], [[1quo]], [[1qsq]], [[261l]], [[262l]], [[259l]], [[220l]], [[222l]], [[223l]], [[225l]], [[226l]], [[227l]], [[228l]], [[229l]], [[235l]], [[236l]], [[237l]], [[238l]], [[239l]], [[240l]], [[241l]], [[242l]], [[243l]], [[244l]], [[245l]], [[246l]], [[247l]], [[248l]], [[249l]], [[250l]], [[251l]], [[252l]], [[253l]], [[254l]], [[255l]], [[230l]], [[231l]], [[232l]], [[233l]], [[234l]], [[209l]], [[210l]], [[211l]], [[212l]], [[213l]], [[214l]], [[215l]], [[218l]], [[219l]], [[180l]], [[195l]], [[196l]], [[197l]], [[198l]], [[199l]], [[200l]], [[190l]], [[191l]], [[192l]], [[189l]], [[155l]], [[156l]], [[157l]], [[158l]], [[159l]], [[160l]], [[161l]], [[162l]], [[163l]], [[164l]], [[165l]], [[166l]], [[129l]], [[130l]], [[131l]], [[140l]], [[141l]], [[142l]], [[143l]], [[144l]], [[145l]], [[146l]], [[147l]], [[201l]], [[205l]], [[221l]], [[224l]], [[102l]], [[103l]], [[104l]], [[107l]], [[108l]], [[109l]], [[110l]], [[111l]], [[112l]], [[113l]], [[114l]], [[115l]], [[118l]], [[119l]], [[120l]], [[122l]], [[123l]], [[125l]], [[126l]], [[127l]], [[128l]], [[1dya]], [[1dyb]], [[1dyc]], [[1dyd]], [[1dye]], [[1dyf]], [[1dyg]], [[1l00]], [[1l85]], [[1l86]], [[1l87]], [[1l88]], [[1l89]], [[1l90]], [[1l91]], [[1l92]], [[1l93]], [[1l94]], [[1l95]], [[1l96]], [[1l97]], [[1l98]], [[1l99]], [[1lye]], [[1lyf]], [[1lyg]], [[1lyh]], [[1lyi]], [[1lyj]], [[217l]], [[1tla]], [[1l77]], [[1l79]], [[1l80]], [[1l81]], [[1l82]], [[2l78]], [[1l36]], [[1l37]], [[1l38]], [[1l39]], [[1l40]], [[1l41]], [[1l42]], [[1l43]], [[1l44]], [[1l45]], [[1l46]], [[1l47]], [[1l48]], [[1l49]], [[1l50]], [[1l51]], [[1l52]], [[1l53]], [[1l54]], [[1l55]], [[1l56]], [[1l57]], [[1l58]], [[1l59]], [[1l60]], [[1l61]], [[1l62]], [[1l63]], [[1l64]], [[1l65]], [[1l66]], [[1l67]], [[1l68]], [[1l69]], [[1l70]], [[1l71]], [[1l72]], [[1l73]], [[1l74]], [[1l75]], [[1l76]], [[1l17]], [[1l18]], [[1l19]], [[1l20]], [[1l21]], [[1l22]], [[1l23]], [[1l24]], [[1l25]], [[1l26]], [[1l27]], [[1l28]], [[1l29]], [[1l30]], [[1l31]], [[1l32]], [[1l33]], [[1l34]], [[1l35]], [[3lzm]], [[1l01]], [[1l02]], [[1l03]], [[1l04]], [[1l05]], [[1l06]], [[1l07]], [[1l08]], [[1l09]], [[1l10]], [[1l11]], [[1l12]], [[1l13]], [[1l14]], [[1l15]], [[1l16]] – T4Lys (mutant) 
[[1c60]], [[1c61]], [[1c62]], [[1c63]], [[1c64]], [[1c65]], [[1c66]], [[1c67]], [[1c68]], [[1c69]], [[1c6a]], [[1c6b]], [[1c6c]], [[1c6d]], [[1c6e]], [[1c6f]], [[1c6g]], [[1c6h]], [[1c6i]], [[1c6j]], [[1c6k]], [[1c6l]], [[1c6m]], [[1c6n]], [[1c6p]], [[1c6q]], [[1c6t]] - T4Lys (mutant) + noble gas 
[[3ht6]], [[3ht7]], [[3ht8]], [[3ht9]], [[3htb]], [[3hu8]], [[3huq]], [[3guj]], [[3guk]], [[3gul]], [[3gum]], [[3gun]], [[3guo]], [[3gup]], [[3dmx]], [[3dmz]], [[3dn0]], [[3dn1]], [[3dn2]], [[3dn3]], [[3dn4]], [[3dn6]], [[3dn8]], [[3dna]], [[2rb1]], [[2ray]], [[2raz]], [[2rb0]], [[2rb2]], [[2rbn]], [[2rbo]], [[2rbq]], [[2rbr]], [[2rbs]], [[2oty]],[[2otz]], [[1owy]], [[1owz]], [[1ov5]], [[1ov7]], [[1ovh]], [[1ovj]], [[1ovk]], [[1lgw]], [[1lgx]], [[1li2]], [[1li3]], [[1l83]], [[1l84]] – T4Lys (mutant) + benzene derivative 
[[3htd]], [[3htf]], [[3htg]], [[3hu9]], [[3hua]], [[3huk]], [[3hh3]], [[3hh4]], [[3hh5]], [[3hh6]], [[2rbp]], [[2ou0]], [[2f2q]], [[2f32]], [[2f47]], [[1xep]] – T4Lys (mutant) + inhibitor 
[[148l]] - T4Lys (mutant) + glucoside 
[[3d3d]], [[1d9u]] – lamLys + chitohexasaccharide 
[[1am7]] – lamLys - Enterobacteria phage λ 
[[2anv]], [[2anx]] – Lys (mutant)]] - Enterobacteria phage p22 
[[1xjt]], [[1xju]] - Lys - Enterobacteria phage p1 
[[1lba]] - T7Lys - Enterobacteria phage T7 

===Lys protein complex===

[[3m18]], [[3g3a]], [[3g3b]] - HEWL + Variable lymphocyte receptor – Marine lamprey 
[[3a67]], [[3a6b]], [[3a6c]], [[2yss]], [[2eiz]], [[2dqc]], [[2dqd]], [[2dqe]], [[2dqf]], [[2dqg]], [[2dqh]], [[2dqi]], [[2dqj]], [[1j1o]], [[1j1p]], [[1j1x]], [[1ic4]], [[1ic5]], [[1ic7]] – HEWL + mLys antibody HYHEL-10 (mutant) 
[[1xgp]], [[1xgq]], [[1xgr]], [[1xgt]], [[1xgu]] – HEWL + mLys antibody HYHEL-63 
[[3d9a]], [[2eks]], [[1ua6]], [[1c08]], [[3hfm]] – HEWL + mLys antibody HYHEL-10 
[[1uac]] - tuLys C + mLys antibody HYHEL-10 
[[1yqv]], [[2iff]] – HEWL + mLys antibody HYHEL-5 
[[1bql]] – BqLys + mLys antibody HYHEL-5 
[[1ndg]] – HEWL + mLys antibody HYHEL-8 
[[1ndm]] – HEWL + mLys antibody HYHEL-26 
[[1dqj]] - HEWL + mLys antibody HYHEL-63 
[[1nby]], [[1nbz]] – HEWL (mutant) + mLys antibody HYHEL-63 
[[1g7h]], [[1g7i]], [[1g7j]], [[1g7l]], [[1g7m]], [[1kip]], [[1kiq]], [[1kir]] – HEWL + mAnti-HEWL monoclonal antibody (mutant) 
[[1mlc]], [[1vfb]] - HEWL + mIGG1-κ D44.1 FAB 
[[1a2y]] - HEWL (mutant) + mIGG1-κ D1.3 FV 
[[1fdl]] - HEWL + mIGG1-κ D1.3 FAB 
[[1jhl]] – phLys + mIGG1-κ D11.15 FV 
[[1fbi]] – GfLys + mIGG1 F9.13.7 FAB 
[[2znw]], [[2znx]] – HEWL + hSCFV10 antibody 
[[1bvk]] - HEWL + hAnti Lys FV antibody 
[[1dzb]] – tuLys + mSCFV 1F9 
[[1zv5]], [[1zvh]], [[1zvy]], [[1zmy]], [[1ri8]], [[1rjc]], [[1xfp]], [[1jtp]], [[1jtt]], [[1jto]], [[1mel]] - HEWL + cAntibody heavy chain domain – camel 
[[1op9]] - hLys C + cAntibody heavy chain domain 
[[3otp]] – HEWL + EcProtease DO – ''Escherichia coli'' 
[[3f6z]] - HEWL + MLIC – ''Pseudomonas aeruginosa'' 
[[3eba]] – hLys C + hCABHUL6 
[[2qb0]], [[2qar]] – T4Lys/E80 TELSAM domain 
[[2i25]], [[2i26]] - HEWL +NsAntigen receptor PBLA8 variable domain – Nurse shark 
[[1sq2]], [[1t6v]] – HEWL +NsNew Antigen receptor variable domain 
[[1gpq]] – HEWL + EcInhibitor of Vertebrate Lys 
[[1aro]] – T7Lys + T7 RNA polymerase 

===Some Useful External Links===
[http://en.wikipedia.org/wiki/Lysozyme Lysozyme]

[http://en.wikipedia.org/wiki/Glycoside_hydrolase#Retaining_glycoside_hydrolases Retaining Glycoside Hydrolases]

===References===
<references/>

Hen Egg-White (HEW) Lysozyme

2011-03-31T01:33:12Z

Anne Goodling:

'''Introduction'''

Lysozyme - also known as muramidase, or glycoside hydrolase - is a powerful enzyme of biological significance found in abundance in tears, saliva, and human milk. In humans, it is encoded in the ''LYZ'' gene. Although it is responsible for the initial digestion of starches in the mouth, it is most widely identified as a non-specific defense in gram positive bacteria and in many species of fungi. Due to its antibacterial effects, it is a strong component of the innate immune system, and is an important part of an infant's diet to ward off diarrheal diseases. Since it is a small, easily available, and highly stable protein containing only 129 amino acid residues, it has been subject to extensive research regarding its function and structure. Hen Egg White (HEW) Lysozyme is shown below.

===History===

Lysozyme is an enzyme known for its unique ability to degrade the polysaccharide architecture of many kinds of cell walls, normally for the purpose of protection against bacterial infection<ref>Lysozyme. 2010. Citizendium.org. http://en.citizendium.org/wiki/Lysozyme</ref>. Its effects were first noticed by Laschtschenko in 1909. It was officially characterized and termed “lysozyme” by Alexander Fleming, the same person credited for the accidental discovery of penicillin.
The characterization of lysozyme in 1922 by Alexander Fleming was providential in that the undertaken experiment related to the discovery of lysozyme was not geared toward any knowledge of such a protein as lysozyme <ref>Lysozyme. 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>. During the unrelated experiment, nasal drippings were inadvertently introduced to a petri dish containing a bacterial culture, which culture consequently exhibited the results of an as yet unknown enzymatic reaction. The observation of this unknown reaction led to further research on the components of this reaction as well as to the corresponding identification of the newfound "lysozyme." Fleming's discovery was complemented by David C. Phillips' 1965 description of the three-dimensional structure of lysozyme via a 200 pm resolution model obtained from X-ray crystallography <ref>Lysozyme, 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>. Phillips' work was especially groundbreaking since Phillips had managed to successfully elucidate the structure of an enzyme via X-ray crystallography - a feat that had never before been accomplished<ref>Bugg, T. 1997. An Introduction to Enzyme and Coenzyme Chemistry. Blackwell Science Ltd., Oxford </ref>. Phillips' research also led to the first sufficiently described enzymatic mechanism of catalytic action <ref>1967. Proc R Soc Lond B Bio 167 (1009): 389–401.</ref>. Thus, Phillips' elucidation of the function of lysozyme led Phillips to reach a more general conclusion on the diversity of enzymatic chemical action in relation to enzymatic structure. Clearly, the findings of Phillips as well as the more general historical development of the understanding of the structure and function of lysozyme have been paramount to the more general realm of enzyme chemistry.

[[Image:nag-nam2.jpg|thumb|left|350px|Lysozyme Cleavage Site]]
<ref>Image from: http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/proteins/lysozyme.htm</ref>

'''Function'''

Lysozyme is known for damaging bacterial cell walls by catalyzing the hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid (NAM) and N-acetyl-D-glucosamine (NAG) residues in peptidoglycan, and between N-acetyl-D-glucosamine residues in chitodextrins. In this way, lysozyme is efficient in lysing the cell walls of both bacteria and fungi. The location of cleavage for lysozyme on this architectural theme is the β(1-4) glycosidic linkage connecting the C1 carbon of NAM to the C4 carbon of NAG.

The particular substrate of preference for this cleavage type is a (NAG-NAM)₃ hexasaccharide, within which substrate occurs the
cleaving target glycosidic bond, NAM₄-β-O-NAG₅. The individual hexasaccharide binding units are designated A-F, with NAM₄-β-O-NAG₅ glycosidic bond cleavage preference corresponding to a D-E unit glycosidic bond cleavage preference.

= Enzymatic Activity of Lysozyme =

Enzymes are designed to attract and to bind specific substrates. The active site of and lysozyme and its specific ligands are described in the following sections

==Mechanistic Features==

'''Zymogen of Lysozyme: Enzymatic Precursor'''

Zymogens are inactive enzyme precursors. Enzymes are developed in an inactive way to prevent the enzyme from digesting the cell that produced it. This process also prevents the enzyme from becoming active in the wrong portion of the body. Lysozyme's zymogen, simply titled “pre-lysozyme,” was sequenced in 1977 by R D Palmiter, J Gagnon, L H Ericsson and K A Walsh, and has since been sequenced much more extensively.

[[Image:jrip.jpg|thumb|left|350px|Mechanism of Lysozyme]]
<ref>Image from: http://www.google.com/imgres?imgurl=http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/pics-and-strucs/lysozyme-mech.gif&imgrefurl=http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/proteins/lysozyme.htm&usg=__ormapG4XKg-tR5GrMSOdSMTV4vE=&h=603&w=801&sz=7&hl=en&start=17&zoom=1&tbnid=nvr9gvFrUILDkM:&tbnh=143&tbnw=189&prev=/images%3Fq%3DThe%2Blysozyme%2Breaction%2Bmechanism%26um%3D1%26hl%3Den%26sa%3DN%26biw%3D1280%26bih%3D647%26tbs%3Disch:10%2C304&um=1&itbs=1&iact=hc&vpx=521&vpy=349&dur=448&hovh=191&hovw=254&tx=140&ty=48&ei=JQ_LTPKzLIjCsAPkzt2KDg&oei=IA_LTP74OsG78gapm-GFAQ&esq=2&page=2&ndsp=18&ved=1t:429,r:2,s:17&biw=1280&bih=647</ref>

'''Mechanism'''

The lysozyme mechanism of action results in the hydrolysis of a glycoside (hence the familial distinction of lysozyme as a glycosylase<ref>Lysozyme, 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>), which corresponds to the conversion of an acetal to a hemiacetal, which reaction (general degradation of glycosidic bond to units "capped" by newly formed hydroxyl groups) necessitates acid catalysis, since the conversion of acetal to hemiacetal involves the protonation of the reactant oxygen prior to actual bond cleavage. <ref>Pratt, C.W., Voet, D., Voet, J.G. Fundamentals of Biochemistry - Life at the Molecular Level - Third Edition. Voet, Voet and Pratt, 2008.</ref>. Furthermore, the transition state obtained from this protonation is a covalent, oxonium ion, intermediate that must obtain resonance stabilization. The need for some means of acid catalysis and covalent resonance stabilization is adequately provided by the Glu 35 and Asp 52 residues of lysozyme, respectively. The reaction mechanism of lysozyme is demonstrated below. In the following image, the reaction begins at the upper left-hand side, and proceeds according to reaction arrows.

As seen to the left, lysozyme works by hydrolyzing the glycosidic bond, distorting the bond between the NAM and NAG. This produces a glycosyl enzyme intermediate, which reacts with a water molecule to produce the product and the unchanged enzyme.

'''Active Site'''

The <scene name='Sandbox_39/Active_site/1'>active site</scene> of lysozyme is formulated as a prominent cleft outlined by the two aforementioned catalytic amino acids, Glu 35 and Asp 52. The active site is geometrically bent to augment ligand binding, and the two amino acids interact with the ligand in the binding site. Asp52 is depicted in green, and Glu35 is depicted in purple.

<applet load='1hew' size='350' frame='true' align='right' caption='' />

==Binding==
'''Ligands'''

A <scene name='Sandbox_39/Ligands_1/1'>ligand</scene> is able to bind to the active site of an enzyme to form a biologically relevant complex. The model to the right shows a space-filling model of lysozyme with the protein distinguishable in brown and the ligand distinguishable in green. Another model of the ligand can be seen in this
<scene name='Sandbox_39/Ribbon_ligand/1'>ribbon diagram</scene>, with the ligand protruding as a space-filling model from the active site. Here, it is clear that the ligand is a polysaccharide.

The lysozyme reaction is characterized by hydrolysis of the beta (1-4) glycosidic bond between NAM and NAG. Lysozyme has a very specific active site, which can bind only six sugar rings from a polysaccharide chain. Once lysozyme binds to this chain, it hydrolyzes them. These six sugar rings represent the ligand of lysozyme. The lysozyme then distorts the fourth sugar in the six-membered complex, producing stress on the molecule and breaking the glycosidic bond.

The amino acid side-chains Glu35 and Asp52 are critical to the activity of this enzyme. Glu35 acts as a proton donor to the glycosidic bond, cleaving the C-O bond in the substrate, and Asp52 acts as a nucleophile to generate a glycosyl enzyme intermediate. The glycosyl enzyme intermediate then reacts with a water molecule to give the product of hydrolysis.

'''Inhibitors'''

Lysozyme is best inhibited by small saccharides which act competitively with the natural substrate. The smaller saccharides will bind to the first three binding sites of the cleft (sites A-C), but will not reach sites D and E, where the enzyme cuts the glycosidic bond. So, the competitive inhibitor will stick in the cleft, not allowing the substrate to bind to the enzyme complex.<ref>http://mcdb-webarchive.mcdb.ucsb.edu/sears/biochemistry/tw-enz/lysozyme/HEWL/lysozyme-overview.htm</ref> Several known inhibitors of lysozyme are: SDS, N-acetyl-D-glucosamine, and various alcohols and oxidizing agents.<ref>http://www.worthington-biochem.com/ly/default.html</ref>

<applet load='1hew' size='350' frame='true' align='left' caption='' />

= Composition and Structure of Lysozyme =

All proteins consist of carbon, hydrogen, nitrogen, oxygen, and sulfur, as do most organic molecules. Enzymes are composed in such a way as to maximize their reactivity with their desired substrate, increasing the efficiency of biological reactions. The <scene name='Sandbox_39/Elements/1'>composition of lysozyme</scene> can be seen on the left, with the carbon atoms outlined in gray, oxygen atoms in red, nitrogen atoms in blue, sulfur atoms in yellow, and the three-letter abbreviation for the <scene name='Sandbox_39/Amino_acid_residues/1'>amino acid residues</scene> in purple.

Lysozyme, like all proteins, also contains a <scene name='Sandbox_39/C_and_n_terminal_residues/1'> 3'C and 5'N terminal </scene>, and these can be seen by following the colors of the rainbow across the molecule. Starting at the red end, the 3' C terminal end, one can work the entire way through to the 5' N terminal end, showing the folding pattern and chain of the protein.

== Secondary Structure ==

Lysozyme contains five <scene name='Sandbox_38/A/2'>alpha helical</scene> regions and five regions containing <scene name='Sandbox_38/B/1'>beta sheets</scene> as displayed in this <scene name='Sandbox_38/Alphab/1'>image</scene>. Linking these secondary structures, a number of beta turns and a large number of random coils make up the remainder of the polypeptide backbone. The polypeptide backbone of lysozyme involved in the 3 antiparallel beta sheets display the beta hairpin motif of supersecondary structure. This depiction of lysozyme contains an antiparallel beta-pleated sheet, which contributes greatly to the stability of the molecule by providing the correct alignment of hydrogen bonds. Lysozyme also contains a great deal of random coil, which is seen in the white regions of the molecule.

==Amino Acid Residues==

The amino acids present in the lysozyme polypeptide sequence have a direct influence not only on primary structure, but also on the secondary and tertiary structures, which can be influenced by polarity and charge of the sidechains. The various amino acid <scene name='Sandbox_38/Aminoi/1'>residues</scene> differ in their properties because of the great variety of side chains present on each amino acid. Polar and nonpolar (and charged and uncharged) side chains lead to various degrees of hydrophobicity and hydrophilicity, which affects protein folding. In lysozyme, these <scene name='Sandbox_38/Sc/1'>side chains</scene> are displayed for each amino acid residue.

= Bonding Interactions =

'''Disulfide Bonding in Lysozyme'''

Lysozyme contains four <scene name='Sandbox_39/Disulfide_bonds/1'>disulfide bonds</scene> involving eight cysteine residues, which are highlighted in yellow on the left. Disulfide bonds are intramolecular forces that stabilize the tertiary structure of many proteins. Disulfide bonds are present in four locations in lysozyme: between Cys 6 and Cys 127, between Cys 30 and Cys 115, between Cys 64 and Cys 80 and between Cys 76 and Cys 94.

'''Hydrogen Bonding'''

In all proteins <scene name='Sandbox_39/Hydrogen_bonds/2'>hydrogen bonds</scene> are essential for stability. In this ribbon diagram, the hydrogen bonds can be seen between the secondary structures of lysozyme highlighted in orange. Since the double bonds of the alpha carbons in the main chain of lysozyme cause torsional strain, lysozyme is limited to very specific hydrogen bonding between the amino acid residues. This representation clearly shows how crucial hydrogen bonding is to help maintain the stability of the protein.

<applet load='1hew' size='350' frame='true' align='left' caption='' />

= Intermolecular Interactions =

'''Hydrophobicity'''

Lysozyme contains both hydrophobic and hydrophilic regions ( <scene name='Sandbox_39/Hydrophobicity/2'>Hydrophobicity</scene> ). The hydrophilic effect, or the desire for proteins to be at a specific position regarding water, is the single most important determinant of protein folding. These regions can be displayed with the hydrophobic regions in gray and the polar, hydrophillic regions in purple. This coloration highlights the location of these regions, showing that the majority of the hydrophobic regions are inside of the protein and that the majority of the hydrophillic regions are on the outside of the protein.

'''Polarity'''

The nature of the amino acid sidechains in the lysozyme polypeptide sequence leads to regions of varying hydrophobicities and polarities of the enzyme structure. The presence of certain regions of hydrophilicity and hydrophobicity is a driving force in determining protein structure when folding. The varying polarities of the side chains influence the locations of residues in the enzyme structure. Nonpolar residues appear blue, and polar residues appear red in the following <scene name='Sandbox_38/Non_polar_blue/1'>polarity</scene> display of lysozyme. Nonpolar residues will display hydrophobic tendencies occurring mostly on the interior of the enzyme while polar residues will increase in abundance on the surface of the protein in order to increase contact with the aqueous solvent so as to satisfy their hydrophilic nature. By observing a space-filled structural depiction of <scene name='Sandbox_38/Non_polar_blu/1'>lysozyme polarity</scene> with polar molecules colored red and nonpolar molecules colored blue the influence of polarity on nucleotide arrangement and protein folding is evident, with the blue (nonpolar) regions inside the red (polar) regions. The presence of <scene name='Sandbox_39/Water/1'>water</scene> interacting with the various hydrophilic residues is depicted to further display how polarity affects structure. Water is depicted as yellow, and the polar and nonpolar regions remain their respective color.

'''Charge'''

Charges of the various regions of the lysozyme structure display a hydrophilic nature and thus also affect the location of that region of polypeptides and the overall folding of the protein. Charged regions of the protein will display hydrophilic tendencies and therefore will most often be located on the surface of the lysozyme molecule where they can interact with the aqueous solvent. Non-charged portions will display hydrophobic tendencies and be located on the interior of the molecule. The effect of various <scene name='Sandbox_38/Rb/1'>charges</scene> on protein structure can be visualized with charged molecules represented by red anionic and blue cationic regions, and uncharged regions colored in grey. This depiction of lysozyme uses a spacefill representation of lysozyme to depict <scene name='Sandbox_38/Chargeddd/1'>charges</scene>.

= Applications of Lysozyme =

Since lysozyme has been widely recognized for its antibacterial and antifungal properties, it has a wide variety of uses both in biochemical and pharmaceutical applications. In molecular biology, lysozyme is often used in the alkaline-lysis procedure for extracting and isolating plasmid DNA. It is used extensively in the pharmaceutical field for destroying gram-positive bacteria, and can be used to support already-existing immune defenses to fight bacterial infections. This enzyme is particularly important for preventing bacterial diseases in infants. Because of its antibacterial properties, lysozyme can also be used in the food industry to help prevent spoilage of foods.

= Discovery and Applications of Hen Egg-White Lysozyme=

<applet load='aln_1H6M_to_1HEW_2.pdb' size='300' frame='true' align='right' caption=' Hen Egg White (HEW) Lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to the active site, PDBid 1HEW' scene='User:Judy_Voet/Lysozyme/Lysozyme1/16' />
Lysozyme was the first enzyme whose X-ray structure was determined <ref> PMID 5840126</ref><ref>Phillips, D. C. The hen egg white lysozyme molecule. Proc. Natl Acad. Sci. USA 57, 483-495 (1967)</ref>. This <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>scene </scene> shows Hen Egg White (HEW) lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to a cleft in the enzyme. David Phillips, who determined the structure in 1965, saw that the cleft was large enough to fit three more saccharide units.
He therefore built a model extending the trisaccharide to a
<scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> that fits into the cleft, labeling the sugar subsites A-F<ref> coordinates of the model kindly provided by Louise Johnson</ref>. Alternately click on <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>trisaccharide</scene> and <scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> to turn the modeled portion of the hexasaccharide on and off.

The interesting thing about the model was that the only way that the hexasaccharide would fit into the cleft was if the 4th saccharide (in subsite D) was strained into a <scene name='User:Judy_Voet/Lysozyme/Half-chair/2'>half-chair conformation</scene>. This conformation is what would be necessary for the formation of an oxocarbenium ion (oxionium ion). When the model was studied, <scene name='User:Judy_Voet/Lysozyme/Glu_35/1'>Glu 35</scene> was found to be in an ideal location to act as a general acid catalyst, 3.34 Angstroms from the bridging oxygen between the 4th and 5th saccharide units. <scene name='User:Judy_Voet/Lysozyme/Asp_52/2'>Asp 52</scene> appeared to be too far away (2.69 angstroms) in the static lysozyme structure to have formed a covalent bond with C1 of the half-chair model in the D site, and no covalent intermediate had ever been detected, so Phillips proposed that it acted as an electrostatic stabilizer of the oxonium ion (referred to as The Phillips Mechanism).

<applet load='aln_1H6M_to_1HEW_2.pdb' size='200' frame='true' align='left' caption='NAG-2-deoxy-2-fluoro-glucosyl fluoride (NAG2FGlcF) bound to Glu35Gln HEW Lysozyme PDBid 1H6M' scene='User:Judy_Voet/Lysozyme/1h6m/3'/>

Then, in 2001, Stephen Withers published <scene name='User:Judy_Voet/Lysozyme/1h6m/3'>1H6M</scene>,<ref>PMID 11518970</ref> in which Glu 35 had been mutated to Gln to remove the general acid catalyst. The substrate contained NAG-2-fluoro-glucosyl fluoride (NAG2FGlcF). The fluoro group on C-1 does not require acid catalysis to be a good leaving group, and the remaining saccharide, in the absence of the acid necessary to catalyse the second step of the reaction, was demonstrated to form a <scene name='User:Judy_Voet/Lysozyme/Covalent/1'> covalent intermediate</scene>. In this <scene name='User:Judy_Voet/Lysozyme/Superposition/2'>superposition</scene> of the half chair model with 1HEW (greens) and the covalent intermediate in 1H6M (blues), note the relatively small motions of Asp 52 and C1 of the sugar ring in going from the model to the covalent intermediate. to observe the motion from the <scene name='User:Judy_Voet/Lysozyme/Asp52_halfchair/1'>half-chair</scene> to the <scene name='User:Judy_Voet/Lysozyme/Covalent/2'>covalent intermediate</scene> just toggle between the two green links.

== 3D Structures of Lysozyme ==

===Lys===

[[2x0a]], [[3iju]], [[3ijv]], [[3a8z]], [[2w1y]], [[2w1m]], [[2w1x]], [[2w1l]], [[3e3d]], [[3exd]], [[2zq3]], [[2zq4]], [[3b72]], [[3b6l]], [[2z12]], [[2z18]], [[2z19]], [[2vb1]], [[2hu3]], [[2hub]], [[2htx]], [[2hu1]], [[2yvb]], [[2epe]], [[2g4p]], [[2g4q]], [[2cgi]], [[2b5z]], [[2d4k]], [[2d91]], [[2f2n]], [[2fbb]], [[2c8o]], [[2c8p]], [[2a6u]], [[2aub]], [[2blx]], [[2bly]], [[2a7d]], [[2a7f]], [[1wtm]], [[1wtn]], [[1w6z]], [[1vdp]], [[1vdq]], [[1vds]], [[1vdt]], [[1ved]], [[1v7t]], [[1ps5]], [[2cds]], [[1lj3]], [[1lj4]], [[1lje]], [[1ljf]], [[1ljg]], [[1ljh]], [[1lji]], [[1ljj]], [[1ljk]], [[1jis]], [[1jit]], [[1jiy]], [[1jj0]], [[1jj1]], [[1jj3]], [[1iee]], [[1qio]], [[1f0w]], [[1f10]], [[1dpx]], [[1c10]], [[1qtk]], [[1lz8]], [[1lz9]], [[1bhz]], [[1bgi]], [[1bwh]], [[1bwi]], [[1bwj]], [[1bvx]], [[1hsw]], [[1hsx]], [[1lpi]], [[4lzt]], [[3lzt]], [[1aki]], [[1jpo]], [[1rfp]], [[193l]], [[194l]], [[5lym]], [[1lza]], [[3lyt]], [[4lyt]], [[5lyt]], [[6lyt]], [[2lzt]], [[1lzt]], [[1lzh]], [[2lzh]], [[7lyz]], [[1lyz]], [[2lyz]], [[3lyz]], [[4lyz]], [[5lyz]], [[6lyz]] - HEWL – chicken 
[[1xei]], [[1xej]], [[1xek]], [[1uco]], [[1lma]], [[4lym]] – HEWL low hydration 
[[1lsa]], [[1lsb]], [[1lsc]], [[1lsd]], [[1lse]], [[1lsf]], [[1lys]] – HEWL temperature influence 
[[2lym]], [[3lym]] – HEWL pressure influence 
[[132l]] – HEWL methylated 
[[1rcm]] – HEWL 3 S-S form 
[[2xbr]], [[2xbs]]- HEWL– Raman crystallography 
[[2zwb]], [[1io5]], [[1lzn]] - HEWL– Neutron 
[[1gxv]], [[1gxx]], [[1e8l]] - HEWL- NMR 
[[2hs7]], [[2hso]], [[2hs9]]- HEWL– Powder diffraction 
[[1ir7]], [[1ir8]], [[1ir9]], [[1ioq]], [[1ior]], [[1ios]], [[1iot]], [[1flq]], [[1flu]], [[1flw]], [[1fly]], [[1fn5]], [[1kxw]], [[1kxx]], [[1kxy]], [[1uia]], [[1uib]], [[1uic]], [[1uid]], [[1uie]], [[1uif]], [[1uig]], [[1uih]], [[1lsm]], [[1lsn]], [[1hel]], [[1hem]], [[1hen]], [[1heo]], [[1hep]], [[1heq]], [[1her]] – HEWL (mutant) 
[[1lyo]], [[2lyo]], [[3lyo]], [[4lyo]] – HEWL cross-linked 
[[1xft]] - tuLys – turkey - Powder diffraction 
[[1jse]], [[1tew]], [[135l]], [[2lz2]], [[1lz2]] – tuLys 
[[3lz2]] – tuLys - Laue 
[[3ab6]] – Lys + NAG3 – Hard clam 
[[2x8r]] – Lys GH25 – ''Aspergillus fumigatus'' 
[[3mgw]] – Lys G – Atlantic salmon 
[[3gxk]], [[3gxr]] – Lys G + NAG – Atlantic cod 
[[2fbd]] – HfLys 1 
[[3cb7]] – HfLys 2 
[[2zij]], [[2zik]], [[2zil]], [[2nwd]], [[1iwt]], [[1iwu]], [[1iwv]], [[1iww]], [[1iwx]], [[1iwy]], [[1iwz]], [[1jwr]], [[1jsf]], [[1rex]], [[1lz1]] – hLys – human 
[[1w08]], [[1ix0]], [[1ioc]], [[1ip1]], [[1ip2]], [[1ip3]], [[1ip4]], [[1ip5]], [[1ip6]], [[1ip7]], [[1qsw]], [[1gev]], [[1gez]], [[1gf0]], [[1gf3]], [[1gf4]], [[1gf5]], [[1gf6]], [[1gf7]], [[1i1z]], [[1i20]], [[1i22]], [[1gfr]], [[1gft]], [[1gfu]], [[1gfv]], [[1gf8]], [[1gf9]], [[1gfa]], [[1gfe]], [[1gfg]], [[1gfh]], [[1gfj]], [[1gfk]], [[1inu]], [[1gdx]], [[1ge0]], [[1ge1]], [[1ge2]], [[1ge3]], [[1ge4]], [[1gdw]], [[1gaz]], [[1gb0]], [[1gb2]], [[1gb3]], [[1gb5]], [[1gb6]], [[1gb7]], [[1gb8]], [[1gb9]], [[1gbo]], [[1gbw]], [[1gbx]], [[1gby]], [[1gbz]], [[1gay]], [[1eq4]], [[1eq5]], [[1eqe]], [[1c7p]], [[1di3]], [[1di4]], [[1di5]], [[1c43]], [[1c45]], [[1c46]], [[1ckg]], [[1cj6]], [[1cj7]], [[1cj8]], [[1cj9]], [[1ckc]], [[1ckd]], [[1ckf]], [[1ckh]], [[1b5z]], [[1b70]], [[1b7q]], [[1b7r]], [[1b7s]], [[1b7l]], [[1b7m]], [[1b7n]], [[1b7p]], [[1b5u]], [[1b5v]], [[1b5w]], [[1b5x]], [[1b5y]], [[1bb3]], [[1bb4]], [[2bqa]], [[2bqb]], [[2bqc]], [[2bqd]], [[2bqe]], [[2bqf]], [[2bqg]], [[2bqh]], [[2bqi]], [[2bqj]], [[2bqk]], [[2bql]], [[2bqm]], [[2bqn]], [[2bqo]], [[2mea]], [[2meb]], [[2mec]], [[2med]], [[2mee]], [[2mef]], [[2meg]], [[2meh]], [[2mei]], [[1wqm]], [[1wqn]], [[1wqo]], [[1wqp]], [[1wqq]], [[1wqr]], [[2heb]], [[2hea]], [[2hec]], [[2hed]], [[2hee]], [[2hef]], [[1jka]], [[1jkb]], [[1jkc]], [[1jkd]], [[1loz]], [[1lyy]], [[1oua]], [[1oub]], [[1ouc]], [[1oud]], [[1oue]], [[1ouf]], [[1oug]], [[1ouh]], [[1oui]], [[1ouj]], [[207l]], [[208l ]], [[1yam]], [[1yan]], [[1yao]], [[1yap]], [[1yaq]], [[1lmt]], [[1lhh]], [[1lhi]], [[1lhj]], [[1lhk]], [[1lhl]], [[133l]], [[134l]], [[1lz4]], [[1lz5]], [[1lz6]], [[1laa]], [[1tay]], [[1tby]], [[1tcy]], [[1tdy]], [[2lhm]], [[3lhm]] – hLys (mutant) 
[[1iy3]], [[1iy4]] – hLys - NMR 
[[2z2f]] – Lys – Bovine 
[[2cwi]], [[1el1]], [[1qqy]] – dLys - dog 
[[2z2e]] – dLys (mutant) 
[[1i56]] – dLys – NMR 
[[2dqa]] – Lys – ''Tapes japonica'' 
[[2gv0]] – Lys – Soft-shelled turtle 
[[1ivm]] – mLys M – NMR – mouse 
[[1jfx]] – Lys – ''Streptomyces coelicolor'' 
[[1gd6]] – Lys – ''Bombyx mori'' 
[[1jug]] – Lys – Echidna 
[[1dkj]] – BqLys – Bobwhite quail 
[[2ihl]] – Lys – Japanese quail 
[[1gbs]] – BsLys – Black swan 
[[1lmn]] – RtLys – Rainbow trout 
[[2eql]] – Lys – horse 
[[1ghl]] – phLys – pheasant 
[[1hhl]] – GfLys – Guinea fowl 
[[1lhm]] – Lys (mutant) – yeast 

===Lys small molecules complexes===

[[3fe0]], [[2d4i]], [[2d4j]], [[1v7s]] - HEWL+ D2O 
[[3m3u]] – HEWL Trp fluorescence 
[[2xjw]] - HEWL + CO 
[[1hf4]], [[1lks]] – HEWL + NO3 
[[3a34]], [[3ems]] - HEWL + arginine 
[[2xth]] – cLys + inhibitor K2PtBr6 
[[3a90]], [[3a91]], [[3a92]], [[3a93]], [[3a94]], [[3a95]], [[3a96]], [[3kam]], [[2pc2]], [[2bpu]], [[1t3p]], [[1h87]] – HEWL + rare earth 
[[2d6b]], [[2hg0]], [[1vat]], [[1gwd]], [[1b2k]], [[1lkr]], [[1azf]], [[8lyz]]- HEWL+ halogen 
[[1vat]] - HEWL + Xe 
[[1n4f]] - HEWL + As 
[[2i6z]] - HEWL + Pt drug 
[[2zyp]] - HEWL + poly (allyl amine) 
[[2f30]], [[2f4a]] – HEWL + urea derivative 
[[2f4g]], [[1ykx]], [[1yky]], [[1ykz]], [[1yl0]], [[1yl1]], [[1z55]] - HEWL + alcohol 
[[1dpw]] – HEWL + MPD 
[[1lcn]] – HEWL + SCN 
[[2zxs]] - HEWL with glycine-amide 
[[2h9j]], [[2h9k]], [[1yik]], [[1yil]] - HEWL + cyclam derivative 
[[1b0d]] – HEWL + p-toluene-sulfonate 
[[2q0m]] - HEWL + tricarbonylmanganese 
[[2war]] – HEWL (mutant) + chitopentaose 
[[2h5z]] – HfLys 1 + chitotetraose – House fly 
[[1hnl]] – hLys + glutathione 
[[1dkk]] – BqLys + NO3 

===Lys complex with glucoside===

[[3a3q]] – HEWL (mutant) + NAG 
[[1sf4]], [[1sf6]], [[1sf7]], [[1sfb]], [[1sfg]], [[1ja2]], [[1ja4]], [[1ja6]], [[1ja7]] – HEWL + NAG oligosaccharide – Powder diffraction 
[[1ubz]], [[1d6p]], [[1d6q]], [[1bb5]] – hLys (mutant) + glycoside 
[[1uc0]], [[1re2]], [[1rem]], [[1rey]], [[1rez]], [[1lzr]], [[1lzs]] - hLys + glycoside 
[[1ljn]], [[1jef]], [[1lzy]] – tuLys + glycoside 
[[1h6m]], [[1at5]], [[1at6]], [[1lzb]], [[1lzc]], [[1lzd]], [[1lze]], [[1lzg]], [[1hew ]]– HEWL + glycoside 
[[1lsy]], [[1lsz]] - HEWL (mutant) + glycoside 
[[1bb6]], [[1bb7]] – RtLys + glycoside 
[[1lmc]] – RtLys + bulgecin 
[[1lmo]], [[1lmp]], [[1lmq]] – RtLys + glucoside 
[[1lsp]] – BsLys + bulgecin 
[[153l]], [[154l]] – Lys +glucoside – goose 

===Phage Lys===

[[2oe4]], [[2oe7]], [[2oe9]], [[2oea]], [[1swz]], [[1cx6]], [[1qtc]], [[1qtd]], [[1qth]], [[1qsb]], [[1qs5]], [[1qs9]], [[1qtb]], [[256l]], [[206l]], [[167l]], [[168l]], [[169l]], [[170l]], [[171l]], [[172l]], [[173l]], [[174l]], [[175l]], [[176l]], [[177l]], [[178l]], [[181l]], [[182l]], [[183l]], [[184l]], [[185l]], [[186l]], [[187l]], [[188l]], [[1nhb]], [[137l]], [[216l]], [[152l]], [[149l]], [[150l]], [[151l]], [[1lyd]], [[2lzm]] - T4Lys – Enterobacteria phage T4 
[[138l]] – T4Lys cross-linked 
[[4lzm]], [[5lzm]], [[6lzm]], [[7lzm]] – T4Lys ionic strength 
[[3l2x]], [[3k2r]], [[3g3v]], [[3g3w]], [[3g3x]], [[2q9d]], [[2q9e]], [[2igc]], [[2ntg]], [[2nth]], [[2ou8]], [[2ou9]], [[1zur]], [[1zwn]], [[1zyt]], [[2cuu]], [[2a4t]] – T4Lys (mutant) spin labeled 
[[3l64]], [[3hwl]], [[3jr6]], [[3gui]], [[3c7w]], [[3c7y]], [[3c7z]], [[3c80]], [[3c81]], [[3c82]], [[3c83]], [[3c8q]], [[3c8r]], [[3c8s]], [[3cdo]], [[3cdq]], [[3cdr]], [[3cdt]], [[3cdv]], [[3f8v]], [[3f9l]], [[3fa0]], [[3fad]], [[3fi5]], [[3dke]], [[3dmv]], [[2o4w]], [[2o79]], [[2o7a]], [[2huk]], [[2hul]], [[2hum]], [[2b7x]], [[2b6t]], [[2b6w]], [[2b6x]], [[2b6y]], [[2b6z]], [[2b70]], [[2b72]], [[2b73]], [[2b74]], [[2b75]], [[1sx7]], [[1swy]], [[1sx2]], [[1t6h]], [[1ssw]], [[1ssy]], [[1t8f]], [[1t8g]], [[1t8a]], [[1t97]], [[1p56]], [[1p5c]], [[1p2l]], [[1p2r]], [[1p36]], [[1p37]], [[1p3n]], [[1p46]], [[1p64]], [[1p6y]], [[1p7s]], [[1pqd]], [[1pqi]], [[1pqj]], [[1pqk]], [[1pqm]], [[1pqo]], [[1oyu]], [[1ks3]], [[1kw5]], [[1kw7]], [[1ky0]], [[1ky1]], [[1l0j]], [[1l0k]], [[1lw9]], [[1lwg]], [[1lwk]], [[1lpy]], [[1llh]], [[1lgu]], [[1li6]], [[1jtm]], [[1jtn]], [[1jqu]], [[1kni]], [[1g06]], [[1g07]], [[1g0g]], [[1g0j]], [[1g0k]], [[1g0l]], [[1g0m]], [[1g0p]], [[1g0q]], [[1g1v]], [[1g1w]], [[1i6s]], [[257l]], [[258l]], [[260l]], [[1epy]], [[1b6i]], [[1cu6]], [[1d9w]], [[1ctw]], [[1cu0]], [[1cu2]], [[1cu3]], [[1cu5]], [[1cv1]], [[1cv4]], [[1cv5]], [[1cv6]], [[1cvk]], [[1cx7]], [[1d2w]], [[1d2y]], [[1d3f]], [[1d3j]], [[1d3m]], [[1d3n]], [[1cv3]], [[1qt3]], [[1qt4]], [[1qt5]], [[1qt6]], [[1qt7]], [[1qt8]], [[1qtv]], [[1qtz]], [[1qud]], [[1qug]], [[1quh]], [[1quo]], [[1qsq]], [[261l]], [[262l]], [[259l]], [[220l]], [[222l]], [[223l]], [[225l]], [[226l]], [[227l]], [[228l]], [[229l]], [[235l]], [[236l]], [[237l]], [[238l]], [[239l]], [[240l]], [[241l]], [[242l]], [[243l]], [[244l]], [[245l]], [[246l]], [[247l]], [[248l]], [[249l]], [[250l]], [[251l]], [[252l]], [[253l]], [[254l]], [[255l]], [[230l]], [[231l]], [[232l]], [[233l]], [[234l]], [[209l]], [[210l]], [[211l]], [[212l]], [[213l]], [[214l]], [[215l]], [[218l]], [[219l]], [[180l]], [[195l]], [[196l]], [[197l]], [[198l]], [[199l]], [[200l]], [[190l]], [[191l]], [[192l]], [[189l]], [[155l]], [[156l]], [[157l]], [[158l]], [[159l]], [[160l]], [[161l]], [[162l]], [[163l]], [[164l]], [[165l]], [[166l]], [[129l]], [[130l]], [[131l]], [[140l]], [[141l]], [[142l]], [[143l]], [[144l]], [[145l]], [[146l]], [[147l]], [[201l]], [[205l]], [[221l]], [[224l]], [[102l]], [[103l]], [[104l]], [[107l]], [[108l]], [[109l]], [[110l]], [[111l]], [[112l]], [[113l]], [[114l]], [[115l]], [[118l]], [[119l]], [[120l]], [[122l]], [[123l]], [[125l]], [[126l]], [[127l]], [[128l]], [[1dya]], [[1dyb]], [[1dyc]], [[1dyd]], [[1dye]], [[1dyf]], [[1dyg]], [[1l00]], [[1l85]], [[1l86]], [[1l87]], [[1l88]], [[1l89]], [[1l90]], [[1l91]], [[1l92]], [[1l93]], [[1l94]], [[1l95]], [[1l96]], [[1l97]], [[1l98]], [[1l99]], [[1lye]], [[1lyf]], [[1lyg]], [[1lyh]], [[1lyi]], [[1lyj]], [[217l]], [[1tla]], [[1l77]], [[1l79]], [[1l80]], [[1l81]], [[1l82]], [[2l78]], [[1l36]], [[1l37]], [[1l38]], [[1l39]], [[1l40]], [[1l41]], [[1l42]], [[1l43]], [[1l44]], [[1l45]], [[1l46]], [[1l47]], [[1l48]], [[1l49]], [[1l50]], [[1l51]], [[1l52]], [[1l53]], [[1l54]], [[1l55]], [[1l56]], [[1l57]], [[1l58]], [[1l59]], [[1l60]], [[1l61]], [[1l62]], [[1l63]], [[1l64]], [[1l65]], [[1l66]], [[1l67]], [[1l68]], [[1l69]], [[1l70]], [[1l71]], [[1l72]], [[1l73]], [[1l74]], [[1l75]], [[1l76]], [[1l17]], [[1l18]], [[1l19]], [[1l20]], [[1l21]], [[1l22]], [[1l23]], [[1l24]], [[1l25]], [[1l26]], [[1l27]], [[1l28]], [[1l29]], [[1l30]], [[1l31]], [[1l32]], [[1l33]], [[1l34]], [[1l35]], [[3lzm]], [[1l01]], [[1l02]], [[1l03]], [[1l04]], [[1l05]], [[1l06]], [[1l07]], [[1l08]], [[1l09]], [[1l10]], [[1l11]], [[1l12]], [[1l13]], [[1l14]], [[1l15]], [[1l16]] – T4Lys (mutant) 
[[1c60]], [[1c61]], [[1c62]], [[1c63]], [[1c64]], [[1c65]], [[1c66]], [[1c67]], [[1c68]], [[1c69]], [[1c6a]], [[1c6b]], [[1c6c]], [[1c6d]], [[1c6e]], [[1c6f]], [[1c6g]], [[1c6h]], [[1c6i]], [[1c6j]], [[1c6k]], [[1c6l]], [[1c6m]], [[1c6n]], [[1c6p]], [[1c6q]], [[1c6t]] - T4Lys (mutant) + noble gas 
[[3ht6]], [[3ht7]], [[3ht8]], [[3ht9]], [[3htb]], [[3hu8]], [[3huq]], [[3guj]], [[3guk]], [[3gul]], [[3gum]], [[3gun]], [[3guo]], [[3gup]], [[3dmx]], [[3dmz]], [[3dn0]], [[3dn1]], [[3dn2]], [[3dn3]], [[3dn4]], [[3dn6]], [[3dn8]], [[3dna]], [[2rb1]], [[2ray]], [[2raz]], [[2rb0]], [[2rb2]], [[2rbn]], [[2rbo]], [[2rbq]], [[2rbr]], [[2rbs]], [[2oty]],[[2otz]], [[1owy]], [[1owz]], [[1ov5]], [[1ov7]], [[1ovh]], [[1ovj]], [[1ovk]], [[1lgw]], [[1lgx]], [[1li2]], [[1li3]], [[1l83]], [[1l84]] – T4Lys (mutant) + benzene derivative 
[[3htd]], [[3htf]], [[3htg]], [[3hu9]], [[3hua]], [[3huk]], [[3hh3]], [[3hh4]], [[3hh5]], [[3hh6]], [[2rbp]], [[2ou0]], [[2f2q]], [[2f32]], [[2f47]], [[1xep]] – T4Lys (mutant) + inhibitor 
[[148l]] - T4Lys (mutant) + glucoside 
[[3d3d]], [[1d9u]] – lamLys + chitohexasaccharide 
[[1am7]] – lamLys - Enterobacteria phage λ 
[[2anv]], [[2anx]] – Lys (mutant)]] - Enterobacteria phage p22 
[[1xjt]], [[1xju]] - Lys - Enterobacteria phage p1 
[[1lba]] - T7Lys - Enterobacteria phage T7 

===Lys protein complex===

[[3m18]], [[3g3a]], [[3g3b]] - HEWL + Variable lymphocyte receptor – Marine lamprey 
[[3a67]], [[3a6b]], [[3a6c]], [[2yss]], [[2eiz]], [[2dqc]], [[2dqd]], [[2dqe]], [[2dqf]], [[2dqg]], [[2dqh]], [[2dqi]], [[2dqj]], [[1j1o]], [[1j1p]], [[1j1x]], [[1ic4]], [[1ic5]], [[1ic7]] – HEWL + mLys antibody HYHEL-10 (mutant) 
[[1xgp]], [[1xgq]], [[1xgr]], [[1xgt]], [[1xgu]] – HEWL + mLys antibody HYHEL-63 
[[3d9a]], [[2eks]], [[1ua6]], [[1c08]], [[3hfm]] – HEWL + mLys antibody HYHEL-10 
[[1uac]] - tuLys C + mLys antibody HYHEL-10 
[[1yqv]], [[2iff]] – HEWL + mLys antibody HYHEL-5 
[[1bql]] – BqLys + mLys antibody HYHEL-5 
[[1ndg]] – HEWL + mLys antibody HYHEL-8 
[[1ndm]] – HEWL + mLys antibody HYHEL-26 
[[1dqj]] - HEWL + mLys antibody HYHEL-63 
[[1nby]], [[1nbz]] – HEWL (mutant) + mLys antibody HYHEL-63 
[[1g7h]], [[1g7i]], [[1g7j]], [[1g7l]], [[1g7m]], [[1kip]], [[1kiq]], [[1kir]] – HEWL + mAnti-HEWL monoclonal antibody (mutant) 
[[1mlc]], [[1vfb]] - HEWL + mIGG1-κ D44.1 FAB 
[[1a2y]] - HEWL (mutant) + mIGG1-κ D1.3 FV 
[[1fdl]] - HEWL + mIGG1-κ D1.3 FAB 
[[1jhl]] – phLys + mIGG1-κ D11.15 FV 
[[1fbi]] – GfLys + mIGG1 F9.13.7 FAB 
[[2znw]], [[2znx]] – HEWL + hSCFV10 antibody 
[[1bvk]] - HEWL + hAnti Lys FV antibody 
[[1dzb]] – tuLys + mSCFV 1F9 
[[1zv5]], [[1zvh]], [[1zvy]], [[1zmy]], [[1ri8]], [[1rjc]], [[1xfp]], [[1jtp]], [[1jtt]], [[1jto]], [[1mel]] - HEWL + cAntibody heavy chain domain – camel 
[[1op9]] - hLys C + cAntibody heavy chain domain 
[[3otp]] – HEWL + EcProtease DO – ''Escherichia coli'' 
[[3f6z]] - HEWL + MLIC – ''Pseudomonas aeruginosa'' 
[[3eba]] – hLys C + hCABHUL6 
[[2qb0]], [[2qar]] – T4Lys/E80 TELSAM domain 
[[2i25]], [[2i26]] - HEWL +NsAntigen receptor PBLA8 variable domain – Nurse shark 
[[1sq2]], [[1t6v]] – HEWL +NsNew Antigen receptor variable domain 
[[1gpq]] – HEWL + EcInhibitor of Vertebrate Lys 
[[1aro]] – T7Lys + T7 RNA polymerase 

===Some Useful External Links===
[http://en.wikipedia.org/wiki/Lysozyme Lysozyme]

[http://en.wikipedia.org/wiki/Glycoside_hydrolase#Retaining_glycoside_hydrolases Retaining Glycoside Hydrolases]

===References===
<references/>

Hen Egg-White (HEW) Lysozyme

2011-03-31T01:29:29Z

Anne Goodling:

'''Introduction'''

Lysozyme - also known as muramidase, or glycoside hydrolase - is a powerful enzyme of biological significance found in abundance in tears, saliva, and human milk. In humans, it is encoded in the ''LYZ'' gene. Although it is responsible for the initial digestion of starches in the mouth, it is most widely identified as a non-specific defense in gram positive bacteria and in many species of fungi. Due to its antibacterial effects, it is a strong component of the innate immune system, and is an important part of an infant's diet to ward off diarrheal diseases. Since it is a small, easily available, and highly stable protein containing only 129 amino acid residues, it has been subject to extensive research regarding its function and structure. Hen Egg White (HEW) Lysozyme is shown below.

===History===

Lysozyme is an enzyme known for its unique ability to degrade the polysaccharide architecture of many kinds of cell walls, normally for the purpose of protection against bacterial infection<ref>Lysozyme. 2010. Citizendium.org. http://en.citizendium.org/wiki/Lysozyme</ref>. Its effects were first noticed by Laschtschenko in 1909. It was officially characterized and termed “lysozyme” by Alexander Fleming, the same person credited for the accidental discovery of penicillin.
The characterization of lysozyme in 1922 by Alexander Fleming was providential in that the undertaken experiment related to the discovery of lysozyme was not geared toward any knowledge of such a protein as lysozyme <ref>Lysozyme. 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>. During the unrelated experiment, nasal drippings were inadvertently introduced to a petri dish containing a bacterial culture, which culture consequently exhibited the results of an as yet unknown enzymatic reaction. The observation of this unknown reaction led to further research on the components of this reaction as well as to the corresponding identification of the newfound "lysozyme." Fleming's discovery was complemented by David C. Phillips' 1965 description of the three-dimensional structure of lysozyme via a 200 pm resolution model obtained from X-ray crystallography <ref>Lysozyme, 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>. Phillips' work was especially groundbreaking since Phillips had managed to successfully elucidate the structure of an enzyme via X-ray crystallography - a feat that had never before been accomplished<ref>Bugg, T. 1997. An Introduction to Enzyme and Coenzyme Chemistry. Blackwell Science Ltd., Oxford </ref>. Phillips' research also led to the first sufficiently described enzymatic mechanism of catalytic action <ref>1967. Proc R Soc Lond B Bio 167 (1009): 389–401.</ref>. Thus, Phillips' elucidation of the function of lysozyme led Phillips to reach a more general conclusion on the diversity of enzymatic chemical action in relation to enzymatic structure. Clearly, the findings of Phillips as well as the more general historical development of the understanding of the structure and function of lysozyme have been paramount to the more general realm of enzyme chemistry.

[[Image:nag-nam2.jpg|thumb|left|350px|Lysozyme Cleavage Site]]
<ref>Image from: http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/proteins/lysozyme.htm</ref>

'''Function'''

Lysozyme is known for damaging bacterial cell walls by catalyzing the hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid (NAM) and N-acetyl-D-glucosamine (NAG) residues in peptidoglycan, and between N-acetyl-D-glucosamine residues in chitodextrins. In this way, lysozyme is efficient in lysing the cell walls of both bacteria and fungi. The location of cleavage for lysozyme on this architectural theme is the β(1-4) glycosidic linkage connecting the C1 carbon of NAM to the C4 carbon of NAG.

The particular substrate of preference for this cleavage type is a (NAG-NAM)₃ hexasaccharide, within which substrate occurs the
cleaving target glycosidic bond, NAM₄-β-O-NAG₅. The individual hexasaccharide binding units are designated A-F, with NAM₄-β-O-NAG₅ glycosidic bond cleavage preference corresponding to a D-E unit glycosidic bond cleavage preference.

= Enzymatic Activity of Lysozyme =

Enzymes are designed to attract and to bind specific substrates. The active site of and lysozyme and its specific ligands are described in the following sections

==Mechanistic Features==

'''Zymogen of Lysozyme: Enzymatic Precursor'''

Zymogens are inactive enzyme precursors. Enzymes are developed in an inactive way to prevent the enzyme from digesting the cell that produced it. This process also prevents the enzyme from becoming active in the wrong portion of the body. Lysozyme's zymogen, simply titled “pre-lysozyme,” was sequenced in 1977 by R D Palmiter, J Gagnon, L H Ericsson and K A Walsh, and has since been sequenced much more extensively.

[[Image:jrip.jpg|thumb|left|350px|Mechanism of Lysozyme]]
<ref>Image from: http://www.google.com/imgres?imgurl=http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/pics-and-strucs/lysozyme-mech.gif&imgrefurl=http://www.vuw.ac.nz/staff/paul_teesdale-spittle/essentials/chapter-6/proteins/lysozyme.htm&usg=__ormapG4XKg-tR5GrMSOdSMTV4vE=&h=603&w=801&sz=7&hl=en&start=17&zoom=1&tbnid=nvr9gvFrUILDkM:&tbnh=143&tbnw=189&prev=/images%3Fq%3DThe%2Blysozyme%2Breaction%2Bmechanism%26um%3D1%26hl%3Den%26sa%3DN%26biw%3D1280%26bih%3D647%26tbs%3Disch:10%2C304&um=1&itbs=1&iact=hc&vpx=521&vpy=349&dur=448&hovh=191&hovw=254&tx=140&ty=48&ei=JQ_LTPKzLIjCsAPkzt2KDg&oei=IA_LTP74OsG78gapm-GFAQ&esq=2&page=2&ndsp=18&ved=1t:429,r:2,s:17&biw=1280&bih=647</ref>

'''Mechanism'''

The lysozyme mechanism of action results in the hydrolysis of a glycoside (hence the familial distinction of lysozyme as a glycosylase<ref>Lysozyme, 2008. Lysozyme.co.uk. http://lysozyme.co.uk/</ref>), which corresponds to the conversion of an acetal to a hemiacetal, which reaction (general degradation of glycosidic bond to units "capped" by newly formed hydroxyl groups) necessitates acid catalysis, since the conversion of acetal to hemiacetal involves the protonation of the reactant oxygen prior to actual bond cleavage. <ref>Pratt, C.W., Voet, D., Voet, J.G. Fundamentals of Biochemistry - Life at the Molecular Level - Third Edition. Voet, Voet and Pratt, 2008.</ref>. Furthermore, the transition state obtained from this protonation is a covalent, oxonium ion, intermediate that must obtain resonance stabilization. The need for some means of acid catalysis and covalent resonance stabilization is adequately provided by the Glu 35 and Asp 52 residues of lysozyme, respectively. The reaction mechanism of lysozyme is demonstrated below. In the following image, the reaction begins at the upper left-hand side, and proceeds according to reaction arrows.

As seen to the left, lysozyme works by hydrolyzing the glycosidic bond, distorting the bond between the NAM and NAG. This produces a glycosyl enzyme intermediate, which reacts with a water molecule to produce the product and the unchanged enzyme.

'''Active Site'''

The <scene name='Sandbox_39/Active_site/1'>active site</scene> of lysozyme is formulated as a prominent cleft outlined by the two aforementioned catalytic amino acids, Glu 35 and Asp 52. The active site is geometrically bent to augment ligand binding, and the two amino acids interact with the ligand in the binding site. Asp52 is depicted in green, and Glu35 is depicted in purple.

<applet load='1hew' size='350' frame='true' align='right' caption='' />

==Binding==
'''Ligands'''

A <scene name='Sandbox_39/Ligands_1/1'>ligand</scene> is able to bind to the active site of an enzyme to form a biologically relevant complex. The model to the right shows a space-filling model of lysozyme with the protein distinguishable in brown and the ligand distinguishable in green. Another model of the ligand can be seen in this
<scene name='Sandbox_39/Ribbon_ligand/1'>ribbon diagram</scene>, with the ligand protruding as a space-filling model from the active site. Here, it is clear that the ligand is a polysaccharide.

The lysozyme reaction is characterized by hydrolysis of the beta (1-4) glycosidic bond between NAM and NAG. Lysozyme has a very specific active site, which can bind only six sugar rings from a polysaccharide chain. Once lysozyme binds to this chain, it hydrolyzes them. These six sugar rings represent the ligand of lysozyme. The lysozyme then distorts the fourth sugar in the six-membered complex, producing stress on the molecule and breaking the glycosidic bond.

The amino acid side-chains Glu35 and Asp52 are critical to the activity of this enzyme. Glu35 acts as a proton donor to the glycosidic bond, cleaving the C-O bond in the substrate, and Asp52 acts as a nucleophile to generate a glycosyl enzyme intermediate. The glycosyl enzyme intermediate then reacts with a water molecule to give the product of hydrolysis.

'''Inhibitors'''

Lysozyme is best inhibited by small saccharides which act competitively with the natural substrate. The smaller saccharides will bind to the first three binding sites of the cleft (sites A-C), but will not reach sites D and E, where the enzyme cuts the glycosidic bond. So, the competitive inhibitor will stick in the cleft, not allowing the substrate to bind to the enzyme complex.<ref>http://mcdb-webarchive.mcdb.ucsb.edu/sears/biochemistry/tw-enz/lysozyme/HEWL/lysozyme-overview.htm</ref> Several known inhibitors of lysozyme are: SDS, N-acetyl-D-glucosamine, and various alcohols and oxidizing agents.<ref>http://www.worthington-biochem.com/ly/default.html</ref>

<applet load='1hew' size='350' frame='true' align='left' caption='' />

= Composition and Structure of Lysozyme =

All proteins consist of carbon, hydrogen, nitrogen, oxygen, and sulfur, as do most organic molecules. Enzymes are composed in such a way as to maximize their reactivity with their desired substrate, increasing the efficiency of biological reactions. The <scene name='Sandbox_39/Elements/1'>composition of lysozyme</scene> can be seen on the left, with the carbon atoms outlined in gray, oxygen atoms in red, nitrogen atoms in blue, sulfur atoms in yellow, and the three-letter abbreviation for the <scene name='Sandbox_39/Amino_acid_residues/1'>amino acid residues</scene> in purple.

Lysozyme, like all proteins, also contains a <scene name='Sandbox_39/C_and_n_terminal_residues/1'> 3'C and 5'N terminal </scene>, and these can be seen by following the colors of the rainbow across the molecule. Starting at the red end, the 3' C terminal end, one can work the entire way through to the 5' N terminal end, showing the folding pattern and chain of the protein.

== Secondary Structure ==

Lysozyme contains five <scene name='Sandbox_38/A/2'>alpha helical</scene> regions and five regions containing <scene name='Sandbox_38/B/1'>beta sheets</scene> as displayed in this <scene name='Sandbox_38/Alphab/1'>image</scene>. Linking these secondary structures, a number of beta turns and a large number of random coils make up the remainder of the polypeptide backbone. The polypeptide backbone of lysozyme involved in the 3 antiparallel beta sheets display the beta hairpin motif of supersecondary structure. This depiction of lysozyme contains an antiparallel beta-pleated sheet, which contributes greatly to the stability of the molecule by providing the correct alignment of hydrogen bonds. Lysozyme also contains a great deal of random coil, which is seen in the white regions of the molecule.

==Amino Acid Residues==

The amino acids present in the lysozyme polypeptide sequence have a direct influence not only on primary structure, but also on the secondary and tertiary structures, which can be influenced by polarity and charge of the sidechains. The various amino acid <scene name='Sandbox_38/Aminoi/1'>residues</scene> differ in their properties because of the great variety of side chains present on each amino acid. Polar and nonpolar (and charged and uncharged) side chains lead to various degrees of hydrophobicity and hydrophilicity, which affects protein folding. In lysozyme, these <scene name='Sandbox_38/Sc/1'>side chains</scene> are displayed for each amino acid residue.

= Bonding Interactions =

'''Disulfide Bonding in Lysozyme'''

Lysozyme contains four <scene name='Sandbox_39/Disulfide_bonds/1'>disulfide bonds</scene> involving eight cysteine residues, which are highlighted in yellow on the left. Disulfide bonds are intramolecular forces that stabilize the tertiary structure of many proteins. Disulfide bonds are present in four locations in lysozyme: between Cys 6 and Cys 127, between Cys 30 and Cys 115, between Cys 64 and Cys 80 and between Cys 76 and Cys 94.

'''Hydrogen Bonding'''

In all proteins <scene name='Sandbox_39/Hydrogen_bonds/2'>hydrogen bonds</scene> are essential for stability. In this ribbon diagram, the hydrogen bonds can be seen between the secondary structures of lysozyme highlighted in orange. Since the double bonds of the alpha carbons in the main chain of lysozyme cause torsional strain, lysozyme is limited to very specific hydrogen bonding between the amino acid residues. This representation clearly shows how crucial hydrogen bonding is to help maintain the stability of the protein.

<applet load='1hew' size='350' frame='true' align='left' caption='' />

= Intermolecular Interactions =

'''Hydrophobicity'''

Lysozyme contains both hydrophobic and hydrophilic regions ( <scene name='Sandbox_39/Hydrophobicity/2'>Hydrophobicity</scene> ). The hydrophilic effect, or the desire for proteins to be at a specific position regarding water, is the single most important determinant of protein folding. These regions can be displayed with the hydrophobic regions in gray and the polar, hydrophillic regions in purple. This coloration highlights the location of these regions, showing that the majority of the hydrophobic regions are inside of the protein and that the majority of the hydrophillic regions are on the outside of the protein.

'''Polarity'''

The nature of the amino acid sidechains in the lysozyme polypeptide sequence leads to regions of varying hydrophobicities and polarities of the enzyme structure. The presence of certain regions of hydrophilicity and hydrophobicity is a driving force in determining protein structure when folding. The varying polarities of the side chains influence the locations of residues in the enzyme structure. Nonpolar residues appear blue, and polar residues appear red in the following <scene name='Sandbox_38/Non_polar_blue/1'>polarity</scene> display of lysozyme. Nonpolar residues will display hydrophobic tendencies occurring mostly on the interior of the enzyme while polar residues will increase in abundance on the surface of the protein in order to increase contact with the aqueous solvent so as to satisfy their hydrophilic nature. By observing a space-filled structural depiction of <scene name='Sandbox_38/Non_polar_blu/1'>lysozyme polarity</scene> with polar molecules colored red and nonpolar molecules colored blue the influence of polarity on nucleotide arrangement and protein folding is evident, with the blue (nonpolar) regions inside the red (polar) regions. The presence of <scene name='Sandbox_39/Water/1'>water</scene> interacting with the various hydrophilic residues is depicted to further display how polarity affects structure. Water is depicted as yellow, and the polar and nonpolar regions remain their respective color.

'''Charge'''

Charges of the various regions of the lysozyme structure display a hydrophilic nature and thus also affect the location of that region of polypeptides and the overall folding of the protein. Charged regions of the protein will display hydrophilic tendencies and therefore will most often be located on the surface of the lysozyme molecule where they can interact with the aqueous solvent. Non-charged portions will display hydrophobic tendencies and be located on the interior of the molecule. The effect of various <scene name='Sandbox_38/Rb/1'>charges</scene> on protein structure can be visualized with charged molecules represented by red anionic and blue cationic regions, and uncharged regions colored in grey. This depiction of lysozyme uses a spacefill representation of lysozyme to depict <scene name='Sandbox_38/Chargeddd/1'>charges</scene>.

= Applications of Lysozyme =

Since lysozyme has been widely recognized for its antibacterial and antifungal properties, it has a wide variety of uses both in biochemical and pharmaceutical applications. In molecular biology, lysozyme is often used in the alkaline-lysis procedure for extracting and isolating plasmid DNA. It is used extensively in the pharmaceutical field for destroying gram-positive bacteria, and can be used to support already-existing immune defenses to fight bacterial infections. This enzyme is particularly important for preventing bacterial diseases in infants. Because of its antibacterial properties, lysozyme can also be used in the food industry to help prevent spoilage of foods.

=== Discovery and Applications of Hen Egg-White Lysozyme===

<applet load='aln_1H6M_to_1HEW_2.pdb' size='300' frame='true' align='right' caption=' Hen Egg White (HEW) Lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to the active site, PDBid 1HEW' scene='User:Judy_Voet/Lysozyme/Lysozyme1/16' />
Lysozyme was the first enzyme whose X-ray structure was determined <ref> PMID 5840126</ref><ref>Phillips, D. C. The hen egg white lysozyme molecule. Proc. Natl Acad. Sci. USA 57, 483-495 (1967)</ref>. This <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>scene </scene> shows Hen Egg White (HEW) lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to a cleft in the enzyme. David Phillips, who determined the structure in 1965, saw that the cleft was large enough to fit three more saccharide units.
He therefore built a model extending the trisaccharide to a
<scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> that fits into the cleft, labeling the sugar subsites A-F<ref> coordinates of the model kindly provided by Louise Johnson</ref>. Alternately click on <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>trisaccharide</scene> and <scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> to turn the modeled portion of the hexasaccharide on and off.

The interesting thing about the model was that the only way that the hexasaccharide would fit into the cleft was if the 4th saccharide (in subsite D) was strained into a <scene name='User:Judy_Voet/Lysozyme/Half-chair/2'>half-chair conformation</scene>. This conformation is what would be necessary for the formation of an oxocarbenium ion (oxionium ion). When the model was studied, <scene name='User:Judy_Voet/Lysozyme/Glu_35/1'>Glu 35</scene> was found to be in an ideal location to act as a general acid catalyst, 3.34 Angstroms from the bridging oxygen between the 4th and 5th saccharide units. <scene name='User:Judy_Voet/Lysozyme/Asp_52/2'>Asp 52</scene> appeared to be too far away (2.69 angstroms) in the static lysozyme structure to have formed a covalent bond with C1 of the half-chair model in the D site, and no covalent intermediate had ever been detected, so Phillips proposed that it acted as an electrostatic stabilizer of the oxonium ion (referred to as The Phillips Mechanism).
<applet load='aln_1H6M_to_1HEW_2.pdb' size='200' frame='true' align='left' caption='NAG-2-deoxy-2-fluoro-glucosyl fluoride (NAG2FGlcF) bound to Glu35Gln HEW Lysozyme PDBid 1H6M' scene='User:Judy_Voet/Lysozyme/1h6m/3'/>

Then, in 2001, Stephen Withers published <scene name='User:Judy_Voet/Lysozyme/1h6m/3'>1H6M</scene>,<ref>PMID 11518970</ref> in which Glu 35 had been mutated to Gln to remove the general acid catalyst. The substrate contained NAG-2-fluoro-glucosyl fluoride (NAG2FGlcF). The fluoro group on C-1 does not require acid catalysis to be a good leaving group, and the remaining saccharide, in the absence of the acid necessary to catalyse the second step of the reaction, was demonstrated to form a <scene name='User:Judy_Voet/Lysozyme/Covalent/1'> covalent intermediate</scene>. In this <scene name='User:Judy_Voet/Lysozyme/Superposition/2'>superposition</scene> of the half chair model with 1HEW (greens) and the covalent intermediate in 1H6M (blues), note the relatively small motions of Asp 52 and C1 of the sugar ring in going from the model to the covalent intermediate. to observe the motion from the <scene name='User:Judy_Voet/Lysozyme/Asp52_halfchair/1'>half-chair</scene> to the <scene name='User:Judy_Voet/Lysozyme/Covalent/2'>covalent intermediate</scene> just toggle between the two green links.

== 3D Structures of Lysozyme ==

===Lys===

[[2x0a]], [[3iju]], [[3ijv]], [[3a8z]], [[2w1y]], [[2w1m]], [[2w1x]], [[2w1l]], [[3e3d]], [[3exd]], [[2zq3]], [[2zq4]], [[3b72]], [[3b6l]], [[2z12]], [[2z18]], [[2z19]], [[2vb1]], [[2hu3]], [[2hub]], [[2htx]], [[2hu1]], [[2yvb]], [[2epe]], [[2g4p]], [[2g4q]], [[2cgi]], [[2b5z]], [[2d4k]], [[2d91]], [[2f2n]], [[2fbb]], [[2c8o]], [[2c8p]], [[2a6u]], [[2aub]], [[2blx]], [[2bly]], [[2a7d]], [[2a7f]], [[1wtm]], [[1wtn]], [[1w6z]], [[1vdp]], [[1vdq]], [[1vds]], [[1vdt]], [[1ved]], [[1v7t]], [[1ps5]], [[2cds]], [[1lj3]], [[1lj4]], [[1lje]], [[1ljf]], [[1ljg]], [[1ljh]], [[1lji]], [[1ljj]], [[1ljk]], [[1jis]], [[1jit]], [[1jiy]], [[1jj0]], [[1jj1]], [[1jj3]], [[1iee]], [[1qio]], [[1f0w]], [[1f10]], [[1dpx]], [[1c10]], [[1qtk]], [[1lz8]], [[1lz9]], [[1bhz]], [[1bgi]], [[1bwh]], [[1bwi]], [[1bwj]], [[1bvx]], [[1hsw]], [[1hsx]], [[1lpi]], [[4lzt]], [[3lzt]], [[1aki]], [[1jpo]], [[1rfp]], [[193l]], [[194l]], [[5lym]], [[1lza]], [[3lyt]], [[4lyt]], [[5lyt]], [[6lyt]], [[2lzt]], [[1lzt]], [[1lzh]], [[2lzh]], [[7lyz]], [[1lyz]], [[2lyz]], [[3lyz]], [[4lyz]], [[5lyz]], [[6lyz]] - HEWL – chicken 
[[1xei]], [[1xej]], [[1xek]], [[1uco]], [[1lma]], [[4lym]] – HEWL low hydration 
[[1lsa]], [[1lsb]], [[1lsc]], [[1lsd]], [[1lse]], [[1lsf]], [[1lys]] – HEWL temperature influence 
[[2lym]], [[3lym]] – HEWL pressure influence 
[[132l]] – HEWL methylated 
[[1rcm]] – HEWL 3 S-S form 
[[2xbr]], [[2xbs]]- HEWL– Raman crystallography 
[[2zwb]], [[1io5]], [[1lzn]] - HEWL– Neutron 
[[1gxv]], [[1gxx]], [[1e8l]] - HEWL- NMR 
[[2hs7]], [[2hso]], [[2hs9]]- HEWL– Powder diffraction 
[[1ir7]], [[1ir8]], [[1ir9]], [[1ioq]], [[1ior]], [[1ios]], [[1iot]], [[1flq]], [[1flu]], [[1flw]], [[1fly]], [[1fn5]], [[1kxw]], [[1kxx]], [[1kxy]], [[1uia]], [[1uib]], [[1uic]], [[1uid]], [[1uie]], [[1uif]], [[1uig]], [[1uih]], [[1lsm]], [[1lsn]], [[1hel]], [[1hem]], [[1hen]], [[1heo]], [[1hep]], [[1heq]], [[1her]] – HEWL (mutant) 
[[1lyo]], [[2lyo]], [[3lyo]], [[4lyo]] – HEWL cross-linked 
[[1xft]] - tuLys – turkey - Powder diffraction 
[[1jse]], [[1tew]], [[135l]], [[2lz2]], [[1lz2]] – tuLys 
[[3lz2]] – tuLys - Laue 
[[3ab6]] – Lys + NAG3 – Hard clam 
[[2x8r]] – Lys GH25 – ''Aspergillus fumigatus'' 
[[3mgw]] – Lys G – Atlantic salmon 
[[3gxk]], [[3gxr]] – Lys G + NAG – Atlantic cod 
[[2fbd]] – HfLys 1 
[[3cb7]] – HfLys 2 
[[2zij]], [[2zik]], [[2zil]], [[2nwd]], [[1iwt]], [[1iwu]], [[1iwv]], [[1iww]], [[1iwx]], [[1iwy]], [[1iwz]], [[1jwr]], [[1jsf]], [[1rex]], [[1lz1]] – hLys – human 
[[1w08]], [[1ix0]], [[1ioc]], [[1ip1]], [[1ip2]], [[1ip3]], [[1ip4]], [[1ip5]], [[1ip6]], [[1ip7]], [[1qsw]], [[1gev]], [[1gez]], [[1gf0]], [[1gf3]], [[1gf4]], [[1gf5]], [[1gf6]], [[1gf7]], [[1i1z]], [[1i20]], [[1i22]], [[1gfr]], [[1gft]], [[1gfu]], [[1gfv]], [[1gf8]], [[1gf9]], [[1gfa]], [[1gfe]], [[1gfg]], [[1gfh]], [[1gfj]], [[1gfk]], [[1inu]], [[1gdx]], [[1ge0]], [[1ge1]], [[1ge2]], [[1ge3]], [[1ge4]], [[1gdw]], [[1gaz]], [[1gb0]], [[1gb2]], [[1gb3]], [[1gb5]], [[1gb6]], [[1gb7]], [[1gb8]], [[1gb9]], [[1gbo]], [[1gbw]], [[1gbx]], [[1gby]], [[1gbz]], [[1gay]], [[1eq4]], [[1eq5]], [[1eqe]], [[1c7p]], [[1di3]], [[1di4]], [[1di5]], [[1c43]], [[1c45]], [[1c46]], [[1ckg]], [[1cj6]], [[1cj7]], [[1cj8]], [[1cj9]], [[1ckc]], [[1ckd]], [[1ckf]], [[1ckh]], [[1b5z]], [[1b70]], [[1b7q]], [[1b7r]], [[1b7s]], [[1b7l]], [[1b7m]], [[1b7n]], [[1b7p]], [[1b5u]], [[1b5v]], [[1b5w]], [[1b5x]], [[1b5y]], [[1bb3]], [[1bb4]], [[2bqa]], [[2bqb]], [[2bqc]], [[2bqd]], [[2bqe]], [[2bqf]], [[2bqg]], [[2bqh]], [[2bqi]], [[2bqj]], [[2bqk]], [[2bql]], [[2bqm]], [[2bqn]], [[2bqo]], [[2mea]], [[2meb]], [[2mec]], [[2med]], [[2mee]], [[2mef]], [[2meg]], [[2meh]], [[2mei]], [[1wqm]], [[1wqn]], [[1wqo]], [[1wqp]], [[1wqq]], [[1wqr]], [[2heb]], [[2hea]], [[2hec]], [[2hed]], [[2hee]], [[2hef]], [[1jka]], [[1jkb]], [[1jkc]], [[1jkd]], [[1loz]], [[1lyy]], [[1oua]], [[1oub]], [[1ouc]], [[1oud]], [[1oue]], [[1ouf]], [[1oug]], [[1ouh]], [[1oui]], [[1ouj]], [[207l]], [[208l ]], [[1yam]], [[1yan]], [[1yao]], [[1yap]], [[1yaq]], [[1lmt]], [[1lhh]], [[1lhi]], [[1lhj]], [[1lhk]], [[1lhl]], [[133l]], [[134l]], [[1lz4]], [[1lz5]], [[1lz6]], [[1laa]], [[1tay]], [[1tby]], [[1tcy]], [[1tdy]], [[2lhm]], [[3lhm]] – hLys (mutant) 
[[1iy3]], [[1iy4]] – hLys - NMR 
[[2z2f]] – Lys – Bovine 
[[2cwi]], [[1el1]], [[1qqy]] – dLys - dog 
[[2z2e]] – dLys (mutant) 
[[1i56]] – dLys – NMR 
[[2dqa]] – Lys – ''Tapes japonica'' 
[[2gv0]] – Lys – Soft-shelled turtle 
[[1ivm]] – mLys M – NMR – mouse 
[[1jfx]] – Lys – ''Streptomyces coelicolor'' 
[[1gd6]] – Lys – ''Bombyx mori'' 
[[1jug]] – Lys – Echidna 
[[1dkj]] – BqLys – Bobwhite quail 
[[2ihl]] – Lys – Japanese quail 
[[1gbs]] – BsLys – Black swan 
[[1lmn]] – RtLys – Rainbow trout 
[[2eql]] – Lys – horse 
[[1ghl]] – phLys – pheasant 
[[1hhl]] – GfLys – Guinea fowl 
[[1lhm]] – Lys (mutant) – yeast 

===Lys small molecules complexes===

[[3fe0]], [[2d4i]], [[2d4j]], [[1v7s]] - HEWL+ D2O 
[[3m3u]] – HEWL Trp fluorescence 
[[2xjw]] - HEWL + CO 
[[1hf4]], [[1lks]] – HEWL + NO3 
[[3a34]], [[3ems]] - HEWL + arginine 
[[2xth]] – cLys + inhibitor K2PtBr6 
[[3a90]], [[3a91]], [[3a92]], [[3a93]], [[3a94]], [[3a95]], [[3a96]], [[3kam]], [[2pc2]], [[2bpu]], [[1t3p]], [[1h87]] – HEWL + rare earth 
[[2d6b]], [[2hg0]], [[1vat]], [[1gwd]], [[1b2k]], [[1lkr]], [[1azf]], [[8lyz]]- HEWL+ halogen 
[[1vat]] - HEWL + Xe 
[[1n4f]] - HEWL + As 
[[2i6z]] - HEWL + Pt drug 
[[2zyp]] - HEWL + poly (allyl amine) 
[[2f30]], [[2f4a]] – HEWL + urea derivative 
[[2f4g]], [[1ykx]], [[1yky]], [[1ykz]], [[1yl0]], [[1yl1]], [[1z55]] - HEWL + alcohol 
[[1dpw]] – HEWL + MPD 
[[1lcn]] – HEWL + SCN 
[[2zxs]] - HEWL with glycine-amide 
[[2h9j]], [[2h9k]], [[1yik]], [[1yil]] - HEWL + cyclam derivative 
[[1b0d]] – HEWL + p-toluene-sulfonate 
[[2q0m]] - HEWL + tricarbonylmanganese 
[[2war]] – HEWL (mutant) + chitopentaose 
[[2h5z]] – HfLys 1 + chitotetraose – House fly 
[[1hnl]] – hLys + glutathione 
[[1dkk]] – BqLys + NO3 

===Lys complex with glucoside===

[[3a3q]] – HEWL (mutant) + NAG 
[[1sf4]], [[1sf6]], [[1sf7]], [[1sfb]], [[1sfg]], [[1ja2]], [[1ja4]], [[1ja6]], [[1ja7]] – HEWL + NAG oligosaccharide – Powder diffraction 
[[1ubz]], [[1d6p]], [[1d6q]], [[1bb5]] – hLys (mutant) + glycoside 
[[1uc0]], [[1re2]], [[1rem]], [[1rey]], [[1rez]], [[1lzr]], [[1lzs]] - hLys + glycoside 
[[1ljn]], [[1jef]], [[1lzy]] – tuLys + glycoside 
[[1h6m]], [[1at5]], [[1at6]], [[1lzb]], [[1lzc]], [[1lzd]], [[1lze]], [[1lzg]], [[1hew ]]– HEWL + glycoside 
[[1lsy]], [[1lsz]] - HEWL (mutant) + glycoside 
[[1bb6]], [[1bb7]] – RtLys + glycoside 
[[1lmc]] – RtLys + bulgecin 
[[1lmo]], [[1lmp]], [[1lmq]] – RtLys + glucoside 
[[1lsp]] – BsLys + bulgecin 
[[153l]], [[154l]] – Lys +glucoside – goose 

===Phage Lys===

[[2oe4]], [[2oe7]], [[2oe9]], [[2oea]], [[1swz]], [[1cx6]], [[1qtc]], [[1qtd]], [[1qth]], [[1qsb]], [[1qs5]], [[1qs9]], [[1qtb]], [[256l]], [[206l]], [[167l]], [[168l]], [[169l]], [[170l]], [[171l]], [[172l]], [[173l]], [[174l]], [[175l]], [[176l]], [[177l]], [[178l]], [[181l]], [[182l]], [[183l]], [[184l]], [[185l]], [[186l]], [[187l]], [[188l]], [[1nhb]], [[137l]], [[216l]], [[152l]], [[149l]], [[150l]], [[151l]], [[1lyd]], [[2lzm]] - T4Lys – Enterobacteria phage T4 
[[138l]] – T4Lys cross-linked 
[[4lzm]], [[5lzm]], [[6lzm]], [[7lzm]] – T4Lys ionic strength 
[[3l2x]], [[3k2r]], [[3g3v]], [[3g3w]], [[3g3x]], [[2q9d]], [[2q9e]], [[2igc]], [[2ntg]], [[2nth]], [[2ou8]], [[2ou9]], [[1zur]], [[1zwn]], [[1zyt]], [[2cuu]], [[2a4t]] – T4Lys (mutant) spin labeled 
[[3l64]], [[3hwl]], [[3jr6]], [[3gui]], [[3c7w]], [[3c7y]], [[3c7z]], [[3c80]], [[3c81]], [[3c82]], [[3c83]], [[3c8q]], [[3c8r]], [[3c8s]], [[3cdo]], [[3cdq]], [[3cdr]], [[3cdt]], [[3cdv]], [[3f8v]], [[3f9l]], [[3fa0]], [[3fad]], [[3fi5]], [[3dke]], [[3dmv]], [[2o4w]], [[2o79]], [[2o7a]], [[2huk]], [[2hul]], [[2hum]], [[2b7x]], [[2b6t]], [[2b6w]], [[2b6x]], [[2b6y]], [[2b6z]], [[2b70]], [[2b72]], [[2b73]], [[2b74]], [[2b75]], [[1sx7]], [[1swy]], [[1sx2]], [[1t6h]], [[1ssw]], [[1ssy]], [[1t8f]], [[1t8g]], [[1t8a]], [[1t97]], [[1p56]], [[1p5c]], [[1p2l]], [[1p2r]], [[1p36]], [[1p37]], [[1p3n]], [[1p46]], [[1p64]], [[1p6y]], [[1p7s]], [[1pqd]], [[1pqi]], [[1pqj]], [[1pqk]], [[1pqm]], [[1pqo]], [[1oyu]], [[1ks3]], [[1kw5]], [[1kw7]], [[1ky0]], [[1ky1]], [[1l0j]], [[1l0k]], [[1lw9]], [[1lwg]], [[1lwk]], [[1lpy]], [[1llh]], [[1lgu]], [[1li6]], [[1jtm]], [[1jtn]], [[1jqu]], [[1kni]], [[1g06]], [[1g07]], [[1g0g]], [[1g0j]], [[1g0k]], [[1g0l]], [[1g0m]], [[1g0p]], [[1g0q]], [[1g1v]], [[1g1w]], [[1i6s]], [[257l]], [[258l]], [[260l]], [[1epy]], [[1b6i]], [[1cu6]], [[1d9w]], [[1ctw]], [[1cu0]], [[1cu2]], [[1cu3]], [[1cu5]], [[1cv1]], [[1cv4]], [[1cv5]], [[1cv6]], [[1cvk]], [[1cx7]], [[1d2w]], [[1d2y]], [[1d3f]], [[1d3j]], [[1d3m]], [[1d3n]], [[1cv3]], [[1qt3]], [[1qt4]], [[1qt5]], [[1qt6]], [[1qt7]], [[1qt8]], [[1qtv]], [[1qtz]], [[1qud]], [[1qug]], [[1quh]], [[1quo]], [[1qsq]], [[261l]], [[262l]], [[259l]], [[220l]], [[222l]], [[223l]], [[225l]], [[226l]], [[227l]], [[228l]], [[229l]], [[235l]], [[236l]], [[237l]], [[238l]], [[239l]], [[240l]], [[241l]], [[242l]], [[243l]], [[244l]], [[245l]], [[246l]], [[247l]], [[248l]], [[249l]], [[250l]], [[251l]], [[252l]], [[253l]], [[254l]], [[255l]], [[230l]], [[231l]], [[232l]], [[233l]], [[234l]], [[209l]], [[210l]], [[211l]], [[212l]], [[213l]], [[214l]], [[215l]], [[218l]], [[219l]], [[180l]], [[195l]], [[196l]], [[197l]], [[198l]], [[199l]], [[200l]], [[190l]], [[191l]], [[192l]], [[189l]], [[155l]], [[156l]], [[157l]], [[158l]], [[159l]], [[160l]], [[161l]], [[162l]], [[163l]], [[164l]], [[165l]], [[166l]], [[129l]], [[130l]], [[131l]], [[140l]], [[141l]], [[142l]], [[143l]], [[144l]], [[145l]], [[146l]], [[147l]], [[201l]], [[205l]], [[221l]], [[224l]], [[102l]], [[103l]], [[104l]], [[107l]], [[108l]], [[109l]], [[110l]], [[111l]], [[112l]], [[113l]], [[114l]], [[115l]], [[118l]], [[119l]], [[120l]], [[122l]], [[123l]], [[125l]], [[126l]], [[127l]], [[128l]], [[1dya]], [[1dyb]], [[1dyc]], [[1dyd]], [[1dye]], [[1dyf]], [[1dyg]], [[1l00]], [[1l85]], [[1l86]], [[1l87]], [[1l88]], [[1l89]], [[1l90]], [[1l91]], [[1l92]], [[1l93]], [[1l94]], [[1l95]], [[1l96]], [[1l97]], [[1l98]], [[1l99]], [[1lye]], [[1lyf]], [[1lyg]], [[1lyh]], [[1lyi]], [[1lyj]], [[217l]], [[1tla]], [[1l77]], [[1l79]], [[1l80]], [[1l81]], [[1l82]], [[2l78]], [[1l36]], [[1l37]], [[1l38]], [[1l39]], [[1l40]], [[1l41]], [[1l42]], [[1l43]], [[1l44]], [[1l45]], [[1l46]], [[1l47]], [[1l48]], [[1l49]], [[1l50]], [[1l51]], [[1l52]], [[1l53]], [[1l54]], [[1l55]], [[1l56]], [[1l57]], [[1l58]], [[1l59]], [[1l60]], [[1l61]], [[1l62]], [[1l63]], [[1l64]], [[1l65]], [[1l66]], [[1l67]], [[1l68]], [[1l69]], [[1l70]], [[1l71]], [[1l72]], [[1l73]], [[1l74]], [[1l75]], [[1l76]], [[1l17]], [[1l18]], [[1l19]], [[1l20]], [[1l21]], [[1l22]], [[1l23]], [[1l24]], [[1l25]], [[1l26]], [[1l27]], [[1l28]], [[1l29]], [[1l30]], [[1l31]], [[1l32]], [[1l33]], [[1l34]], [[1l35]], [[3lzm]], [[1l01]], [[1l02]], [[1l03]], [[1l04]], [[1l05]], [[1l06]], [[1l07]], [[1l08]], [[1l09]], [[1l10]], [[1l11]], [[1l12]], [[1l13]], [[1l14]], [[1l15]], [[1l16]] – T4Lys (mutant) 
[[1c60]], [[1c61]], [[1c62]], [[1c63]], [[1c64]], [[1c65]], [[1c66]], [[1c67]], [[1c68]], [[1c69]], [[1c6a]], [[1c6b]], [[1c6c]], [[1c6d]], [[1c6e]], [[1c6f]], [[1c6g]], [[1c6h]], [[1c6i]], [[1c6j]], [[1c6k]], [[1c6l]], [[1c6m]], [[1c6n]], [[1c6p]], [[1c6q]], [[1c6t]] - T4Lys (mutant) + noble gas 
[[3ht6]], [[3ht7]], [[3ht8]], [[3ht9]], [[3htb]], [[3hu8]], [[3huq]], [[3guj]], [[3guk]], [[3gul]], [[3gum]], [[3gun]], [[3guo]], [[3gup]], [[3dmx]], [[3dmz]], [[3dn0]], [[3dn1]], [[3dn2]], [[3dn3]], [[3dn4]], [[3dn6]], [[3dn8]], [[3dna]], [[2rb1]], [[2ray]], [[2raz]], [[2rb0]], [[2rb2]], [[2rbn]], [[2rbo]], [[2rbq]], [[2rbr]], [[2rbs]], [[2oty]],[[2otz]], [[1owy]], [[1owz]], [[1ov5]], [[1ov7]], [[1ovh]], [[1ovj]], [[1ovk]], [[1lgw]], [[1lgx]], [[1li2]], [[1li3]], [[1l83]], [[1l84]] – T4Lys (mutant) + benzene derivative 
[[3htd]], [[3htf]], [[3htg]], [[3hu9]], [[3hua]], [[3huk]], [[3hh3]], [[3hh4]], [[3hh5]], [[3hh6]], [[2rbp]], [[2ou0]], [[2f2q]], [[2f32]], [[2f47]], [[1xep]] – T4Lys (mutant) + inhibitor 
[[148l]] - T4Lys (mutant) + glucoside 
[[3d3d]], [[1d9u]] – lamLys + chitohexasaccharide 
[[1am7]] – lamLys - Enterobacteria phage λ 
[[2anv]], [[2anx]] – Lys (mutant)]] - Enterobacteria phage p22 
[[1xjt]], [[1xju]] - Lys - Enterobacteria phage p1 
[[1lba]] - T7Lys - Enterobacteria phage T7 

===Lys protein complex===

[[3m18]], [[3g3a]], [[3g3b]] - HEWL + Variable lymphocyte receptor – Marine lamprey 
[[3a67]], [[3a6b]], [[3a6c]], [[2yss]], [[2eiz]], [[2dqc]], [[2dqd]], [[2dqe]], [[2dqf]], [[2dqg]], [[2dqh]], [[2dqi]], [[2dqj]], [[1j1o]], [[1j1p]], [[1j1x]], [[1ic4]], [[1ic5]], [[1ic7]] – HEWL + mLys antibody HYHEL-10 (mutant) 
[[1xgp]], [[1xgq]], [[1xgr]], [[1xgt]], [[1xgu]] – HEWL + mLys antibody HYHEL-63 
[[3d9a]], [[2eks]], [[1ua6]], [[1c08]], [[3hfm]] – HEWL + mLys antibody HYHEL-10 
[[1uac]] - tuLys C + mLys antibody HYHEL-10 
[[1yqv]], [[2iff]] – HEWL + mLys antibody HYHEL-5 
[[1bql]] – BqLys + mLys antibody HYHEL-5 
[[1ndg]] – HEWL + mLys antibody HYHEL-8 
[[1ndm]] – HEWL + mLys antibody HYHEL-26 
[[1dqj]] - HEWL + mLys antibody HYHEL-63 
[[1nby]], [[1nbz]] – HEWL (mutant) + mLys antibody HYHEL-63 
[[1g7h]], [[1g7i]], [[1g7j]], [[1g7l]], [[1g7m]], [[1kip]], [[1kiq]], [[1kir]] – HEWL + mAnti-HEWL monoclonal antibody (mutant) 
[[1mlc]], [[1vfb]] - HEWL + mIGG1-κ D44.1 FAB 
[[1a2y]] - HEWL (mutant) + mIGG1-κ D1.3 FV 
[[1fdl]] - HEWL + mIGG1-κ D1.3 FAB 
[[1jhl]] – phLys + mIGG1-κ D11.15 FV 
[[1fbi]] – GfLys + mIGG1 F9.13.7 FAB 
[[2znw]], [[2znx]] – HEWL + hSCFV10 antibody 
[[1bvk]] - HEWL + hAnti Lys FV antibody 
[[1dzb]] – tuLys + mSCFV 1F9 
[[1zv5]], [[1zvh]], [[1zvy]], [[1zmy]], [[1ri8]], [[1rjc]], [[1xfp]], [[1jtp]], [[1jtt]], [[1jto]], [[1mel]] - HEWL + cAntibody heavy chain domain – camel 
[[1op9]] - hLys C + cAntibody heavy chain domain 
[[3otp]] – HEWL + EcProtease DO – ''Escherichia coli'' 
[[3f6z]] - HEWL + MLIC – ''Pseudomonas aeruginosa'' 
[[3eba]] – hLys C + hCABHUL6 
[[2qb0]], [[2qar]] – T4Lys/E80 TELSAM domain 
[[2i25]], [[2i26]] - HEWL +NsAntigen receptor PBLA8 variable domain – Nurse shark 
[[1sq2]], [[1t6v]] – HEWL +NsNew Antigen receptor variable domain 
[[1gpq]] – HEWL + EcInhibitor of Vertebrate Lys 
[[1aro]] – T7Lys + T7 RNA polymerase 

===Some Useful External Links===
[http://en.wikipedia.org/wiki/Lysozyme Lysozyme]

[http://en.wikipedia.org/wiki/Glycoside_hydrolase#Retaining_glycoside_hydrolases Retaining Glycoside Hydrolases]

===References===
<references/>

Hen Egg-White (HEW) Lysozyme

2011-03-31T01:25:43Z

Anne Goodling:

=== Discovery and Applications of Hen Egg-White Lysozyme===

<applet load='aln_1H6M_to_1HEW_2.pdb' size='300' frame='true' align='right' caption=' Hen Egg White (HEW) Lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to the active site, PDBid 1HEW' scene='User:Judy_Voet/Lysozyme/Lysozyme1/16' />
Lysozyme was the first enzyme whose X-ray structure was determined <ref> PMID 5840126</ref><ref>Phillips, D. C. The hen egg white lysozyme molecule. Proc. Natl Acad. Sci. USA 57, 483-495 (1967)</ref>. This <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>scene </scene> shows Hen Egg White (HEW) lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to a cleft in the enzyme. David Phillips, who determined the structure in 1965, saw that the cleft was large enough to fit three more saccharide units.
He therefore built a model extending the trisaccharide to a
<scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> that fits into the cleft, labeling the sugar subsites A-F<ref> coordinates of the model kindly provided by Louise Johnson</ref>. Alternately click on <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>trisaccharide</scene> and <scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> to turn the modeled portion of the hexasaccharide on and off.

The interesting thing about the model was that the only way that the hexasaccharide would fit into the cleft was if the 4th saccharide (in subsite D) was strained into a <scene name='User:Judy_Voet/Lysozyme/Half-chair/2'>half-chair conformation</scene>. This conformation is what would be necessary for the formation of an oxocarbenium ion (oxionium ion). When the model was studied, <scene name='User:Judy_Voet/Lysozyme/Glu_35/1'>Glu 35</scene> was found to be in an ideal location to act as a general acid catalyst, 3.34 Angstroms from the bridging oxygen between the 4th and 5th saccharide units. <scene name='User:Judy_Voet/Lysozyme/Asp_52/2'>Asp 52</scene> appeared to be too far away (2.69 angstroms) in the static lysozyme structure to have formed a covalent bond with C1 of the half-chair model in the D site, and no covalent intermediate had ever been detected, so Phillips proposed that it acted as an electrostatic stabilizer of the oxonium ion (referred to as The Phillips Mechanism).
<applet load='aln_1H6M_to_1HEW_2.pdb' size='200' frame='true' align='left' caption='NAG-2-deoxy-2-fluoro-glucosyl fluoride (NAG2FGlcF) bound to Glu35Gln HEW Lysozyme PDBid 1H6M' scene='User:Judy_Voet/Lysozyme/1h6m/3'/>

Then, in 2001, Stephen Withers published <scene name='User:Judy_Voet/Lysozyme/1h6m/3'>1H6M</scene>,<ref>PMID 11518970</ref> in which Glu 35 had been mutated to Gln to remove the general acid catalyst. The substrate contained NAG-2-fluoro-glucosyl fluoride (NAG2FGlcF). The fluoro group on C-1 does not require acid catalysis to be a good leaving group, and the remaining saccharide, in the absence of the acid necessary to catalyse the second step of the reaction, was demonstrated to form a <scene name='User:Judy_Voet/Lysozyme/Covalent/1'> covalent intermediate</scene>. In this <scene name='User:Judy_Voet/Lysozyme/Superposition/2'>superposition</scene> of the half chair model with 1HEW (greens) and the covalent intermediate in 1H6M (blues), note the relatively small motions of Asp 52 and C1 of the sugar ring in going from the model to the covalent intermediate. to observe the motion from the <scene name='User:Judy_Voet/Lysozyme/Asp52_halfchair/1'>half-chair</scene> to the <scene name='User:Judy_Voet/Lysozyme/Covalent/2'>covalent intermediate</scene> just toggle between the two green links.

== 3D Structures of Lysozyme ==

===Lys===

[[2x0a]], [[3iju]], [[3ijv]], [[3a8z]], [[2w1y]], [[2w1m]], [[2w1x]], [[2w1l]], [[3e3d]], [[3exd]], [[2zq3]], [[2zq4]], [[3b72]], [[3b6l]], [[2z12]], [[2z18]], [[2z19]], [[2vb1]], [[2hu3]], [[2hub]], [[2htx]], [[2hu1]], [[2yvb]], [[2epe]], [[2g4p]], [[2g4q]], [[2cgi]], [[2b5z]], [[2d4k]], [[2d91]], [[2f2n]], [[2fbb]], [[2c8o]], [[2c8p]], [[2a6u]], [[2aub]], [[2blx]], [[2bly]], [[2a7d]], [[2a7f]], [[1wtm]], [[1wtn]], [[1w6z]], [[1vdp]], [[1vdq]], [[1vds]], [[1vdt]], [[1ved]], [[1v7t]], [[1ps5]], [[2cds]], [[1lj3]], [[1lj4]], [[1lje]], [[1ljf]], [[1ljg]], [[1ljh]], [[1lji]], [[1ljj]], [[1ljk]], [[1jis]], [[1jit]], [[1jiy]], [[1jj0]], [[1jj1]], [[1jj3]], [[1iee]], [[1qio]], [[1f0w]], [[1f10]], [[1dpx]], [[1c10]], [[1qtk]], [[1lz8]], [[1lz9]], [[1bhz]], [[1bgi]], [[1bwh]], [[1bwi]], [[1bwj]], [[1bvx]], [[1hsw]], [[1hsx]], [[1lpi]], [[4lzt]], [[3lzt]], [[1aki]], [[1jpo]], [[1rfp]], [[193l]], [[194l]], [[5lym]], [[1lza]], [[3lyt]], [[4lyt]], [[5lyt]], [[6lyt]], [[2lzt]], [[1lzt]], [[1lzh]], [[2lzh]], [[7lyz]], [[1lyz]], [[2lyz]], [[3lyz]], [[4lyz]], [[5lyz]], [[6lyz]] - HEWL – chicken 
[[1xei]], [[1xej]], [[1xek]], [[1uco]], [[1lma]], [[4lym]] – HEWL low hydration 
[[1lsa]], [[1lsb]], [[1lsc]], [[1lsd]], [[1lse]], [[1lsf]], [[1lys]] – HEWL temperature influence 
[[2lym]], [[3lym]] – HEWL pressure influence 
[[132l]] – HEWL methylated 
[[1rcm]] – HEWL 3 S-S form 
[[2xbr]], [[2xbs]]- HEWL– Raman crystallography 
[[2zwb]], [[1io5]], [[1lzn]] - HEWL– Neutron 
[[1gxv]], [[1gxx]], [[1e8l]] - HEWL- NMR 
[[2hs7]], [[2hso]], [[2hs9]]- HEWL– Powder diffraction 
[[1ir7]], [[1ir8]], [[1ir9]], [[1ioq]], [[1ior]], [[1ios]], [[1iot]], [[1flq]], [[1flu]], [[1flw]], [[1fly]], [[1fn5]], [[1kxw]], [[1kxx]], [[1kxy]], [[1uia]], [[1uib]], [[1uic]], [[1uid]], [[1uie]], [[1uif]], [[1uig]], [[1uih]], [[1lsm]], [[1lsn]], [[1hel]], [[1hem]], [[1hen]], [[1heo]], [[1hep]], [[1heq]], [[1her]] – HEWL (mutant) 
[[1lyo]], [[2lyo]], [[3lyo]], [[4lyo]] – HEWL cross-linked 
[[1xft]] - tuLys – turkey - Powder diffraction 
[[1jse]], [[1tew]], [[135l]], [[2lz2]], [[1lz2]] – tuLys 
[[3lz2]] – tuLys - Laue 
[[3ab6]] – Lys + NAG3 – Hard clam 
[[2x8r]] – Lys GH25 – ''Aspergillus fumigatus'' 
[[3mgw]] – Lys G – Atlantic salmon 
[[3gxk]], [[3gxr]] – Lys G + NAG – Atlantic cod 
[[2fbd]] – HfLys 1 
[[3cb7]] – HfLys 2 
[[2zij]], [[2zik]], [[2zil]], [[2nwd]], [[1iwt]], [[1iwu]], [[1iwv]], [[1iww]], [[1iwx]], [[1iwy]], [[1iwz]], [[1jwr]], [[1jsf]], [[1rex]], [[1lz1]] – hLys – human 
[[1w08]], [[1ix0]], [[1ioc]], [[1ip1]], [[1ip2]], [[1ip3]], [[1ip4]], [[1ip5]], [[1ip6]], [[1ip7]], [[1qsw]], [[1gev]], [[1gez]], [[1gf0]], [[1gf3]], [[1gf4]], [[1gf5]], [[1gf6]], [[1gf7]], [[1i1z]], [[1i20]], [[1i22]], [[1gfr]], [[1gft]], [[1gfu]], [[1gfv]], [[1gf8]], [[1gf9]], [[1gfa]], [[1gfe]], [[1gfg]], [[1gfh]], [[1gfj]], [[1gfk]], [[1inu]], [[1gdx]], [[1ge0]], [[1ge1]], [[1ge2]], [[1ge3]], [[1ge4]], [[1gdw]], [[1gaz]], [[1gb0]], [[1gb2]], [[1gb3]], [[1gb5]], [[1gb6]], [[1gb7]], [[1gb8]], [[1gb9]], [[1gbo]], [[1gbw]], [[1gbx]], [[1gby]], [[1gbz]], [[1gay]], [[1eq4]], [[1eq5]], [[1eqe]], [[1c7p]], [[1di3]], [[1di4]], [[1di5]], [[1c43]], [[1c45]], [[1c46]], [[1ckg]], [[1cj6]], [[1cj7]], [[1cj8]], [[1cj9]], [[1ckc]], [[1ckd]], [[1ckf]], [[1ckh]], [[1b5z]], [[1b70]], [[1b7q]], [[1b7r]], [[1b7s]], [[1b7l]], [[1b7m]], [[1b7n]], [[1b7p]], [[1b5u]], [[1b5v]], [[1b5w]], [[1b5x]], [[1b5y]], [[1bb3]], [[1bb4]], [[2bqa]], [[2bqb]], [[2bqc]], [[2bqd]], [[2bqe]], [[2bqf]], [[2bqg]], [[2bqh]], [[2bqi]], [[2bqj]], [[2bqk]], [[2bql]], [[2bqm]], [[2bqn]], [[2bqo]], [[2mea]], [[2meb]], [[2mec]], [[2med]], [[2mee]], [[2mef]], [[2meg]], [[2meh]], [[2mei]], [[1wqm]], [[1wqn]], [[1wqo]], [[1wqp]], [[1wqq]], [[1wqr]], [[2heb]], [[2hea]], [[2hec]], [[2hed]], [[2hee]], [[2hef]], [[1jka]], [[1jkb]], [[1jkc]], [[1jkd]], [[1loz]], [[1lyy]], [[1oua]], [[1oub]], [[1ouc]], [[1oud]], [[1oue]], [[1ouf]], [[1oug]], [[1ouh]], [[1oui]], [[1ouj]], [[207l]], [[208l ]], [[1yam]], [[1yan]], [[1yao]], [[1yap]], [[1yaq]], [[1lmt]], [[1lhh]], [[1lhi]], [[1lhj]], [[1lhk]], [[1lhl]], [[133l]], [[134l]], [[1lz4]], [[1lz5]], [[1lz6]], [[1laa]], [[1tay]], [[1tby]], [[1tcy]], [[1tdy]], [[2lhm]], [[3lhm]] – hLys (mutant) 
[[1iy3]], [[1iy4]] – hLys - NMR 
[[2z2f]] – Lys – Bovine 
[[2cwi]], [[1el1]], [[1qqy]] – dLys - dog 
[[2z2e]] – dLys (mutant) 
[[1i56]] – dLys – NMR 
[[2dqa]] – Lys – ''Tapes japonica'' 
[[2gv0]] – Lys – Soft-shelled turtle 
[[1ivm]] – mLys M – NMR – mouse 
[[1jfx]] – Lys – ''Streptomyces coelicolor'' 
[[1gd6]] – Lys – ''Bombyx mori'' 
[[1jug]] – Lys – Echidna 
[[1dkj]] – BqLys – Bobwhite quail 
[[2ihl]] – Lys – Japanese quail 
[[1gbs]] – BsLys – Black swan 
[[1lmn]] – RtLys – Rainbow trout 
[[2eql]] – Lys – horse 
[[1ghl]] – phLys – pheasant 
[[1hhl]] – GfLys – Guinea fowl 
[[1lhm]] – Lys (mutant) – yeast 

===Lys small molecules complexes===

[[3fe0]], [[2d4i]], [[2d4j]], [[1v7s]] - HEWL+ D2O 
[[3m3u]] – HEWL Trp fluorescence 
[[2xjw]] - HEWL + CO 
[[1hf4]], [[1lks]] – HEWL + NO3 
[[3a34]], [[3ems]] - HEWL + arginine 
[[2xth]] – cLys + inhibitor K2PtBr6 
[[3a90]], [[3a91]], [[3a92]], [[3a93]], [[3a94]], [[3a95]], [[3a96]], [[3kam]], [[2pc2]], [[2bpu]], [[1t3p]], [[1h87]] – HEWL + rare earth 
[[2d6b]], [[2hg0]], [[1vat]], [[1gwd]], [[1b2k]], [[1lkr]], [[1azf]], [[8lyz]]- HEWL+ halogen 
[[1vat]] - HEWL + Xe 
[[1n4f]] - HEWL + As 
[[2i6z]] - HEWL + Pt drug 
[[2zyp]] - HEWL + poly (allyl amine) 
[[2f30]], [[2f4a]] – HEWL + urea derivative 
[[2f4g]], [[1ykx]], [[1yky]], [[1ykz]], [[1yl0]], [[1yl1]], [[1z55]] - HEWL + alcohol 
[[1dpw]] – HEWL + MPD 
[[1lcn]] – HEWL + SCN 
[[2zxs]] - HEWL with glycine-amide 
[[2h9j]], [[2h9k]], [[1yik]], [[1yil]] - HEWL + cyclam derivative 
[[1b0d]] – HEWL + p-toluene-sulfonate 
[[2q0m]] - HEWL + tricarbonylmanganese 
[[2war]] – HEWL (mutant) + chitopentaose 
[[2h5z]] – HfLys 1 + chitotetraose – House fly 
[[1hnl]] – hLys + glutathione 
[[1dkk]] – BqLys + NO3 

===Lys complex with glucoside===

[[3a3q]] – HEWL (mutant) + NAG 
[[1sf4]], [[1sf6]], [[1sf7]], [[1sfb]], [[1sfg]], [[1ja2]], [[1ja4]], [[1ja6]], [[1ja7]] – HEWL + NAG oligosaccharide – Powder diffraction 
[[1ubz]], [[1d6p]], [[1d6q]], [[1bb5]] – hLys (mutant) + glycoside 
[[1uc0]], [[1re2]], [[1rem]], [[1rey]], [[1rez]], [[1lzr]], [[1lzs]] - hLys + glycoside 
[[1ljn]], [[1jef]], [[1lzy]] – tuLys + glycoside 
[[1h6m]], [[1at5]], [[1at6]], [[1lzb]], [[1lzc]], [[1lzd]], [[1lze]], [[1lzg]], [[1hew ]]– HEWL + glycoside 
[[1lsy]], [[1lsz]] - HEWL (mutant) + glycoside 
[[1bb6]], [[1bb7]] – RtLys + glycoside 
[[1lmc]] – RtLys + bulgecin 
[[1lmo]], [[1lmp]], [[1lmq]] – RtLys + glucoside 
[[1lsp]] – BsLys + bulgecin 
[[153l]], [[154l]] – Lys +glucoside – goose 

===Phage Lys===

[[2oe4]], [[2oe7]], [[2oe9]], [[2oea]], [[1swz]], [[1cx6]], [[1qtc]], [[1qtd]], [[1qth]], [[1qsb]], [[1qs5]], [[1qs9]], [[1qtb]], [[256l]], [[206l]], [[167l]], [[168l]], [[169l]], [[170l]], [[171l]], [[172l]], [[173l]], [[174l]], [[175l]], [[176l]], [[177l]], [[178l]], [[181l]], [[182l]], [[183l]], [[184l]], [[185l]], [[186l]], [[187l]], [[188l]], [[1nhb]], [[137l]], [[216l]], [[152l]], [[149l]], [[150l]], [[151l]], [[1lyd]], [[2lzm]] - T4Lys – Enterobacteria phage T4 
[[138l]] – T4Lys cross-linked 
[[4lzm]], [[5lzm]], [[6lzm]], [[7lzm]] – T4Lys ionic strength 
[[3l2x]], [[3k2r]], [[3g3v]], [[3g3w]], [[3g3x]], [[2q9d]], [[2q9e]], [[2igc]], [[2ntg]], [[2nth]], [[2ou8]], [[2ou9]], [[1zur]], [[1zwn]], [[1zyt]], [[2cuu]], [[2a4t]] – T4Lys (mutant) spin labeled 
[[3l64]], [[3hwl]], [[3jr6]], [[3gui]], [[3c7w]], [[3c7y]], [[3c7z]], [[3c80]], [[3c81]], [[3c82]], [[3c83]], [[3c8q]], [[3c8r]], [[3c8s]], [[3cdo]], [[3cdq]], [[3cdr]], [[3cdt]], [[3cdv]], [[3f8v]], [[3f9l]], [[3fa0]], [[3fad]], [[3fi5]], [[3dke]], [[3dmv]], [[2o4w]], [[2o79]], [[2o7a]], [[2huk]], [[2hul]], [[2hum]], [[2b7x]], [[2b6t]], [[2b6w]], [[2b6x]], [[2b6y]], [[2b6z]], [[2b70]], [[2b72]], [[2b73]], [[2b74]], [[2b75]], [[1sx7]], [[1swy]], [[1sx2]], [[1t6h]], [[1ssw]], [[1ssy]], [[1t8f]], [[1t8g]], [[1t8a]], [[1t97]], [[1p56]], [[1p5c]], [[1p2l]], [[1p2r]], [[1p36]], [[1p37]], [[1p3n]], [[1p46]], [[1p64]], [[1p6y]], [[1p7s]], [[1pqd]], [[1pqi]], [[1pqj]], [[1pqk]], [[1pqm]], [[1pqo]], [[1oyu]], [[1ks3]], [[1kw5]], [[1kw7]], [[1ky0]], [[1ky1]], [[1l0j]], [[1l0k]], [[1lw9]], [[1lwg]], [[1lwk]], [[1lpy]], [[1llh]], [[1lgu]], [[1li6]], [[1jtm]], [[1jtn]], [[1jqu]], [[1kni]], [[1g06]], [[1g07]], [[1g0g]], [[1g0j]], [[1g0k]], [[1g0l]], [[1g0m]], [[1g0p]], [[1g0q]], [[1g1v]], [[1g1w]], [[1i6s]], [[257l]], [[258l]], [[260l]], [[1epy]], [[1b6i]], [[1cu6]], [[1d9w]], [[1ctw]], [[1cu0]], [[1cu2]], [[1cu3]], [[1cu5]], [[1cv1]], [[1cv4]], [[1cv5]], [[1cv6]], [[1cvk]], [[1cx7]], [[1d2w]], [[1d2y]], [[1d3f]], [[1d3j]], [[1d3m]], [[1d3n]], [[1cv3]], [[1qt3]], [[1qt4]], [[1qt5]], [[1qt6]], [[1qt7]], [[1qt8]], [[1qtv]], [[1qtz]], [[1qud]], [[1qug]], [[1quh]], [[1quo]], [[1qsq]], [[261l]], [[262l]], [[259l]], [[220l]], [[222l]], [[223l]], [[225l]], [[226l]], [[227l]], [[228l]], [[229l]], [[235l]], [[236l]], [[237l]], [[238l]], [[239l]], [[240l]], [[241l]], [[242l]], [[243l]], [[244l]], [[245l]], [[246l]], [[247l]], [[248l]], [[249l]], [[250l]], [[251l]], [[252l]], [[253l]], [[254l]], [[255l]], [[230l]], [[231l]], [[232l]], [[233l]], [[234l]], [[209l]], [[210l]], [[211l]], [[212l]], [[213l]], [[214l]], [[215l]], [[218l]], [[219l]], [[180l]], [[195l]], [[196l]], [[197l]], [[198l]], [[199l]], [[200l]], [[190l]], [[191l]], [[192l]], [[189l]], [[155l]], [[156l]], [[157l]], [[158l]], [[159l]], [[160l]], [[161l]], [[162l]], [[163l]], [[164l]], [[165l]], [[166l]], [[129l]], [[130l]], [[131l]], [[140l]], [[141l]], [[142l]], [[143l]], [[144l]], [[145l]], [[146l]], [[147l]], [[201l]], [[205l]], [[221l]], [[224l]], [[102l]], [[103l]], [[104l]], [[107l]], [[108l]], [[109l]], [[110l]], [[111l]], [[112l]], [[113l]], [[114l]], [[115l]], [[118l]], [[119l]], [[120l]], [[122l]], [[123l]], [[125l]], [[126l]], [[127l]], [[128l]], [[1dya]], [[1dyb]], [[1dyc]], [[1dyd]], [[1dye]], [[1dyf]], [[1dyg]], [[1l00]], [[1l85]], [[1l86]], [[1l87]], [[1l88]], [[1l89]], [[1l90]], [[1l91]], [[1l92]], [[1l93]], [[1l94]], [[1l95]], [[1l96]], [[1l97]], [[1l98]], [[1l99]], [[1lye]], [[1lyf]], [[1lyg]], [[1lyh]], [[1lyi]], [[1lyj]], [[217l]], [[1tla]], [[1l77]], [[1l79]], [[1l80]], [[1l81]], [[1l82]], [[2l78]], [[1l36]], [[1l37]], [[1l38]], [[1l39]], [[1l40]], [[1l41]], [[1l42]], [[1l43]], [[1l44]], [[1l45]], [[1l46]], [[1l47]], [[1l48]], [[1l49]], [[1l50]], [[1l51]], [[1l52]], [[1l53]], [[1l54]], [[1l55]], [[1l56]], [[1l57]], [[1l58]], [[1l59]], [[1l60]], [[1l61]], [[1l62]], [[1l63]], [[1l64]], [[1l65]], [[1l66]], [[1l67]], [[1l68]], [[1l69]], [[1l70]], [[1l71]], [[1l72]], [[1l73]], [[1l74]], [[1l75]], [[1l76]], [[1l17]], [[1l18]], [[1l19]], [[1l20]], [[1l21]], [[1l22]], [[1l23]], [[1l24]], [[1l25]], [[1l26]], [[1l27]], [[1l28]], [[1l29]], [[1l30]], [[1l31]], [[1l32]], [[1l33]], [[1l34]], [[1l35]], [[3lzm]], [[1l01]], [[1l02]], [[1l03]], [[1l04]], [[1l05]], [[1l06]], [[1l07]], [[1l08]], [[1l09]], [[1l10]], [[1l11]], [[1l12]], [[1l13]], [[1l14]], [[1l15]], [[1l16]] – T4Lys (mutant) 
[[1c60]], [[1c61]], [[1c62]], [[1c63]], [[1c64]], [[1c65]], [[1c66]], [[1c67]], [[1c68]], [[1c69]], [[1c6a]], [[1c6b]], [[1c6c]], [[1c6d]], [[1c6e]], [[1c6f]], [[1c6g]], [[1c6h]], [[1c6i]], [[1c6j]], [[1c6k]], [[1c6l]], [[1c6m]], [[1c6n]], [[1c6p]], [[1c6q]], [[1c6t]] - T4Lys (mutant) + noble gas 
[[3ht6]], [[3ht7]], [[3ht8]], [[3ht9]], [[3htb]], [[3hu8]], [[3huq]], [[3guj]], [[3guk]], [[3gul]], [[3gum]], [[3gun]], [[3guo]], [[3gup]], [[3dmx]], [[3dmz]], [[3dn0]], [[3dn1]], [[3dn2]], [[3dn3]], [[3dn4]], [[3dn6]], [[3dn8]], [[3dna]], [[2rb1]], [[2ray]], [[2raz]], [[2rb0]], [[2rb2]], [[2rbn]], [[2rbo]], [[2rbq]], [[2rbr]], [[2rbs]], [[2oty]],[[2otz]], [[1owy]], [[1owz]], [[1ov5]], [[1ov7]], [[1ovh]], [[1ovj]], [[1ovk]], [[1lgw]], [[1lgx]], [[1li2]], [[1li3]], [[1l83]], [[1l84]] – T4Lys (mutant) + benzene derivative 
[[3htd]], [[3htf]], [[3htg]], [[3hu9]], [[3hua]], [[3huk]], [[3hh3]], [[3hh4]], [[3hh5]], [[3hh6]], [[2rbp]], [[2ou0]], [[2f2q]], [[2f32]], [[2f47]], [[1xep]] – T4Lys (mutant) + inhibitor 
[[148l]] - T4Lys (mutant) + glucoside 
[[3d3d]], [[1d9u]] – lamLys + chitohexasaccharide 
[[1am7]] – lamLys - Enterobacteria phage λ 
[[2anv]], [[2anx]] – Lys (mutant)]] - Enterobacteria phage p22 
[[1xjt]], [[1xju]] - Lys - Enterobacteria phage p1 
[[1lba]] - T7Lys - Enterobacteria phage T7 

===Lys protein complex===

[[3m18]], [[3g3a]], [[3g3b]] - HEWL + Variable lymphocyte receptor – Marine lamprey 
[[3a67]], [[3a6b]], [[3a6c]], [[2yss]], [[2eiz]], [[2dqc]], [[2dqd]], [[2dqe]], [[2dqf]], [[2dqg]], [[2dqh]], [[2dqi]], [[2dqj]], [[1j1o]], [[1j1p]], [[1j1x]], [[1ic4]], [[1ic5]], [[1ic7]] – HEWL + mLys antibody HYHEL-10 (mutant) 
[[1xgp]], [[1xgq]], [[1xgr]], [[1xgt]], [[1xgu]] – HEWL + mLys antibody HYHEL-63 
[[3d9a]], [[2eks]], [[1ua6]], [[1c08]], [[3hfm]] – HEWL + mLys antibody HYHEL-10 
[[1uac]] - tuLys C + mLys antibody HYHEL-10 
[[1yqv]], [[2iff]] – HEWL + mLys antibody HYHEL-5 
[[1bql]] – BqLys + mLys antibody HYHEL-5 
[[1ndg]] – HEWL + mLys antibody HYHEL-8 
[[1ndm]] – HEWL + mLys antibody HYHEL-26 
[[1dqj]] - HEWL + mLys antibody HYHEL-63 
[[1nby]], [[1nbz]] – HEWL (mutant) + mLys antibody HYHEL-63 
[[1g7h]], [[1g7i]], [[1g7j]], [[1g7l]], [[1g7m]], [[1kip]], [[1kiq]], [[1kir]] – HEWL + mAnti-HEWL monoclonal antibody (mutant) 
[[1mlc]], [[1vfb]] - HEWL + mIGG1-κ D44.1 FAB 
[[1a2y]] - HEWL (mutant) + mIGG1-κ D1.3 FV 
[[1fdl]] - HEWL + mIGG1-κ D1.3 FAB 
[[1jhl]] – phLys + mIGG1-κ D11.15 FV 
[[1fbi]] – GfLys + mIGG1 F9.13.7 FAB 
[[2znw]], [[2znx]] – HEWL + hSCFV10 antibody 
[[1bvk]] - HEWL + hAnti Lys FV antibody 
[[1dzb]] – tuLys + mSCFV 1F9 
[[1zv5]], [[1zvh]], [[1zvy]], [[1zmy]], [[1ri8]], [[1rjc]], [[1xfp]], [[1jtp]], [[1jtt]], [[1jto]], [[1mel]] - HEWL + cAntibody heavy chain domain – camel 
[[1op9]] - hLys C + cAntibody heavy chain domain 
[[3otp]] – HEWL + EcProtease DO – ''Escherichia coli'' 
[[3f6z]] - HEWL + MLIC – ''Pseudomonas aeruginosa'' 
[[3eba]] – hLys C + hCABHUL6 
[[2qb0]], [[2qar]] – T4Lys/E80 TELSAM domain 
[[2i25]], [[2i26]] - HEWL +NsAntigen receptor PBLA8 variable domain – Nurse shark 
[[1sq2]], [[1t6v]] – HEWL +NsNew Antigen receptor variable domain 
[[1gpq]] – HEWL + EcInhibitor of Vertebrate Lys 
[[1aro]] – T7Lys + T7 RNA polymerase 

===Some Useful External Links===
[http://en.wikipedia.org/wiki/Lysozyme Lysozyme]

[http://en.wikipedia.org/wiki/Glycoside_hydrolase#Retaining_glycoside_hydrolases Retaining Glycoside Hydrolases]

===References===
<references/>

Hen Egg-White (HEW) Lysozyme

2011-03-31T01:20:55Z

Anne Goodling:

<applet load='aln_1H6M_to_1HEW_2.pdb' size='300' frame='true' align='right' caption=' Hen Egg White (HEW) Lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to the active site, PDBid 1HEW' scene='User:Judy_Voet/Lysozyme/Lysozyme1/16' />
Lysozyme was the first enzyme whose X-ray structure was determined <ref> PMID 5840126</ref><ref>Phillips, D. C. The hen egg white lysozyme molecule. Proc. Natl Acad. Sci. USA 57, 483-495 (1967)</ref>. This <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>scene </scene> shows Hen Egg White (HEW) lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to a cleft in the enzyme. David Phillips, who determined the structure in 1965, saw that the cleft was large enough to fit three more saccharide units.
He therefore built a model extending the trisaccharide to a
<scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> that fits into the cleft, labeling the sugar subsites A-F<ref> coordinates of the model kindly provided by Louise Johnson</ref>. Alternately click on <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>trisaccharide</scene> and <scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> to turn the modeled portion of the hexasaccharide on and off.

The interesting thing about the model was that the only way that the hexasaccharide would fit into the cleft was if the 4th saccharide (in subsite D) was strained into a <scene name='User:Judy_Voet/Lysozyme/Half-chair/2'>half-chair conformation</scene>. This conformation is what would be necessary for the formation of an oxocarbenium ion (oxionium ion). When the model was studied, <scene name='User:Judy_Voet/Lysozyme/Glu_35/1'>Glu 35</scene> was found to be in an ideal location to act as a general acid catalyst, 3.34 Angstroms from the bridging oxygen between the 4th and 5th saccharide units. <scene name='User:Judy_Voet/Lysozyme/Asp_52/2'>Asp 52</scene> appeared to be too far away (2.69 angstroms) in the static lysozyme structure to have formed a covalent bond with C1 of the half-chair model in the D site, and no covalent intermediate had ever been detected, so Phillips proposed that it acted as an electrostatic stabilizer of the oxonium ion (referred to as The Phillips Mechanism).
<applet load='aln_1H6M_to_1HEW_2.pdb' size='200' frame='true' align='left' caption='NAG-2-deoxy-2-fluoro-glucosyl fluoride (NAG2FGlcF) bound to Glu35Gln HEW Lysozyme PDBid 1H6M' scene='User:Judy_Voet/Lysozyme/1h6m/3'/>

Then, in 2001, Stephen Withers published <scene name='User:Judy_Voet/Lysozyme/1h6m/3'>1H6M</scene>,<ref>PMID 11518970</ref> in which Glu 35 had been mutated to Gln to remove the general acid catalyst. The substrate contained NAG-2-fluoro-glucosyl fluoride (NAG2FGlcF). The fluoro group on C-1 does not require acid catalysis to be a good leaving group, and the remaining saccharide, in the absence of the acid necessary to catalyse the second step of the reaction, was demonstrated to form a <scene name='User:Judy_Voet/Lysozyme/Covalent/1'> covalent intermediate</scene>. In this <scene name='User:Judy_Voet/Lysozyme/Superposition/2'>superposition</scene> of the half chair model with 1HEW (greens) and the covalent intermediate in 1H6M (blues), note the relatively small motions of Asp 52 and C1 of the sugar ring in going from the model to the covalent intermediate. to observe the motion from the <scene name='User:Judy_Voet/Lysozyme/Asp52_halfchair/1'>half-chair</scene> to the <scene name='User:Judy_Voet/Lysozyme/Covalent/2'>covalent intermediate</scene> just toggle between the two green links.

== 3D Structures of Lysozyme ==

===Lys===

[[2x0a]], [[3iju]], [[3ijv]], [[3a8z]], [[2w1y]], [[2w1m]], [[2w1x]], [[2w1l]], [[3e3d]], [[3exd]], [[2zq3]], [[2zq4]], [[3b72]], [[3b6l]], [[2z12]], [[2z18]], [[2z19]], [[2vb1]], [[2hu3]], [[2hub]], [[2htx]], [[2hu1]], [[2yvb]], [[2epe]], [[2g4p]], [[2g4q]], [[2cgi]], [[2b5z]], [[2d4k]], [[2d91]], [[2f2n]], [[2fbb]], [[2c8o]], [[2c8p]], [[2a6u]], [[2aub]], [[2blx]], [[2bly]], [[2a7d]], [[2a7f]], [[1wtm]], [[1wtn]], [[1w6z]], [[1vdp]], [[1vdq]], [[1vds]], [[1vdt]], [[1ved]], [[1v7t]], [[1ps5]], [[2cds]], [[1lj3]], [[1lj4]], [[1lje]], [[1ljf]], [[1ljg]], [[1ljh]], [[1lji]], [[1ljj]], [[1ljk]], [[1jis]], [[1jit]], [[1jiy]], [[1jj0]], [[1jj1]], [[1jj3]], [[1iee]], [[1qio]], [[1f0w]], [[1f10]], [[1dpx]], [[1c10]], [[1qtk]], [[1lz8]], [[1lz9]], [[1bhz]], [[1bgi]], [[1bwh]], [[1bwi]], [[1bwj]], [[1bvx]], [[1hsw]], [[1hsx]], [[1lpi]], [[4lzt]], [[3lzt]], [[1aki]], [[1jpo]], [[1rfp]], [[193l]], [[194l]], [[5lym]], [[1lza]], [[3lyt]], [[4lyt]], [[5lyt]], [[6lyt]], [[2lzt]], [[1lzt]], [[1lzh]], [[2lzh]], [[7lyz]], [[1lyz]], [[2lyz]], [[3lyz]], [[4lyz]], [[5lyz]], [[6lyz]] - HEWL – chicken 
[[1xei]], [[1xej]], [[1xek]], [[1uco]], [[1lma]], [[4lym]] – HEWL low hydration 
[[1lsa]], [[1lsb]], [[1lsc]], [[1lsd]], [[1lse]], [[1lsf]], [[1lys]] – HEWL temperature influence 
[[2lym]], [[3lym]] – HEWL pressure influence 
[[132l]] – HEWL methylated 
[[1rcm]] – HEWL 3 S-S form 
[[2xbr]], [[2xbs]]- HEWL– Raman crystallography 
[[2zwb]], [[1io5]], [[1lzn]] - HEWL– Neutron 
[[1gxv]], [[1gxx]], [[1e8l]] - HEWL- NMR 
[[2hs7]], [[2hso]], [[2hs9]]- HEWL– Powder diffraction 
[[1ir7]], [[1ir8]], [[1ir9]], [[1ioq]], [[1ior]], [[1ios]], [[1iot]], [[1flq]], [[1flu]], [[1flw]], [[1fly]], [[1fn5]], [[1kxw]], [[1kxx]], [[1kxy]], [[1uia]], [[1uib]], [[1uic]], [[1uid]], [[1uie]], [[1uif]], [[1uig]], [[1uih]], [[1lsm]], [[1lsn]], [[1hel]], [[1hem]], [[1hen]], [[1heo]], [[1hep]], [[1heq]], [[1her]] – HEWL (mutant) 
[[1lyo]], [[2lyo]], [[3lyo]], [[4lyo]] – HEWL cross-linked 
[[1xft]] - tuLys – turkey - Powder diffraction 
[[1jse]], [[1tew]], [[135l]], [[2lz2]], [[1lz2]] – tuLys 
[[3lz2]] – tuLys - Laue 
[[3ab6]] – Lys + NAG3 – Hard clam 
[[2x8r]] – Lys GH25 – ''Aspergillus fumigatus'' 
[[3mgw]] – Lys G – Atlantic salmon 
[[3gxk]], [[3gxr]] – Lys G + NAG – Atlantic cod 
[[2fbd]] – HfLys 1 
[[3cb7]] – HfLys 2 
[[2zij]], [[2zik]], [[2zil]], [[2nwd]], [[1iwt]], [[1iwu]], [[1iwv]], [[1iww]], [[1iwx]], [[1iwy]], [[1iwz]], [[1jwr]], [[1jsf]], [[1rex]], [[1lz1]] – hLys – human 
[[1w08]], [[1ix0]], [[1ioc]], [[1ip1]], [[1ip2]], [[1ip3]], [[1ip4]], [[1ip5]], [[1ip6]], [[1ip7]], [[1qsw]], [[1gev]], [[1gez]], [[1gf0]], [[1gf3]], [[1gf4]], [[1gf5]], [[1gf6]], [[1gf7]], [[1i1z]], [[1i20]], [[1i22]], [[1gfr]], [[1gft]], [[1gfu]], [[1gfv]], [[1gf8]], [[1gf9]], [[1gfa]], [[1gfe]], [[1gfg]], [[1gfh]], [[1gfj]], [[1gfk]], [[1inu]], [[1gdx]], [[1ge0]], [[1ge1]], [[1ge2]], [[1ge3]], [[1ge4]], [[1gdw]], [[1gaz]], [[1gb0]], [[1gb2]], [[1gb3]], [[1gb5]], [[1gb6]], [[1gb7]], [[1gb8]], [[1gb9]], [[1gbo]], [[1gbw]], [[1gbx]], [[1gby]], [[1gbz]], [[1gay]], [[1eq4]], [[1eq5]], [[1eqe]], [[1c7p]], [[1di3]], [[1di4]], [[1di5]], [[1c43]], [[1c45]], [[1c46]], [[1ckg]], [[1cj6]], [[1cj7]], [[1cj8]], [[1cj9]], [[1ckc]], [[1ckd]], [[1ckf]], [[1ckh]], [[1b5z]], [[1b70]], [[1b7q]], [[1b7r]], [[1b7s]], [[1b7l]], [[1b7m]], [[1b7n]], [[1b7p]], [[1b5u]], [[1b5v]], [[1b5w]], [[1b5x]], [[1b5y]], [[1bb3]], [[1bb4]], [[2bqa]], [[2bqb]], [[2bqc]], [[2bqd]], [[2bqe]], [[2bqf]], [[2bqg]], [[2bqh]], [[2bqi]], [[2bqj]], [[2bqk]], [[2bql]], [[2bqm]], [[2bqn]], [[2bqo]], [[2mea]], [[2meb]], [[2mec]], [[2med]], [[2mee]], [[2mef]], [[2meg]], [[2meh]], [[2mei]], [[1wqm]], [[1wqn]], [[1wqo]], [[1wqp]], [[1wqq]], [[1wqr]], [[2heb]], [[2hea]], [[2hec]], [[2hed]], [[2hee]], [[2hef]], [[1jka]], [[1jkb]], [[1jkc]], [[1jkd]], [[1loz]], [[1lyy]], [[1oua]], [[1oub]], [[1ouc]], [[1oud]], [[1oue]], [[1ouf]], [[1oug]], [[1ouh]], [[1oui]], [[1ouj]], [[207l]], [[208l ]], [[1yam]], [[1yan]], [[1yao]], [[1yap]], [[1yaq]], [[1lmt]], [[1lhh]], [[1lhi]], [[1lhj]], [[1lhk]], [[1lhl]], [[133l]], [[134l]], [[1lz4]], [[1lz5]], [[1lz6]], [[1laa]], [[1tay]], [[1tby]], [[1tcy]], [[1tdy]], [[2lhm]], [[3lhm]] – hLys (mutant) 
[[1iy3]], [[1iy4]] – hLys - NMR 
[[2z2f]] – Lys – Bovine 
[[2cwi]], [[1el1]], [[1qqy]] – dLys - dog 
[[2z2e]] – dLys (mutant) 
[[1i56]] – dLys – NMR 
[[2dqa]] – Lys – ''Tapes japonica'' 
[[2gv0]] – Lys – Soft-shelled turtle 
[[1ivm]] – mLys M – NMR – mouse 
[[1jfx]] – Lys – ''Streptomyces coelicolor'' 
[[1gd6]] – Lys – ''Bombyx mori'' 
[[1jug]] – Lys – Echidna 
[[1dkj]] – BqLys – Bobwhite quail 
[[2ihl]] – Lys – Japanese quail 
[[1gbs]] – BsLys – Black swan 
[[1lmn]] – RtLys – Rainbow trout 
[[2eql]] – Lys – horse 
[[1ghl]] – phLys – pheasant 
[[1hhl]] – GfLys – Guinea fowl 
[[1lhm]] – Lys (mutant) – yeast 

===Lys small molecules complexes===

[[3fe0]], [[2d4i]], [[2d4j]], [[1v7s]] - HEWL+ D2O 
[[3m3u]] – HEWL Trp fluorescence 
[[2xjw]] - HEWL + CO 
[[1hf4]], [[1lks]] – HEWL + NO3 
[[3a34]], [[3ems]] - HEWL + arginine 
[[2xth]] – cLys + inhibitor K2PtBr6 
[[3a90]], [[3a91]], [[3a92]], [[3a93]], [[3a94]], [[3a95]], [[3a96]], [[3kam]], [[2pc2]], [[2bpu]], [[1t3p]], [[1h87]] – HEWL + rare earth 
[[2d6b]], [[2hg0]], [[1vat]], [[1gwd]], [[1b2k]], [[1lkr]], [[1azf]], [[8lyz]]- HEWL+ halogen 
[[1vat]] - HEWL + Xe 
[[1n4f]] - HEWL + As 
[[2i6z]] - HEWL + Pt drug 
[[2zyp]] - HEWL + poly (allyl amine) 
[[2f30]], [[2f4a]] – HEWL + urea derivative 
[[2f4g]], [[1ykx]], [[1yky]], [[1ykz]], [[1yl0]], [[1yl1]], [[1z55]] - HEWL + alcohol 
[[1dpw]] – HEWL + MPD 
[[1lcn]] – HEWL + SCN 
[[2zxs]] - HEWL with glycine-amide 
[[2h9j]], [[2h9k]], [[1yik]], [[1yil]] - HEWL + cyclam derivative 
[[1b0d]] – HEWL + p-toluene-sulfonate 
[[2q0m]] - HEWL + tricarbonylmanganese 
[[2war]] – HEWL (mutant) + chitopentaose 
[[2h5z]] – HfLys 1 + chitotetraose – House fly 
[[1hnl]] – hLys + glutathione 
[[1dkk]] – BqLys + NO3 

===Lys complex with glucoside===

[[3a3q]] – HEWL (mutant) + NAG 
[[1sf4]], [[1sf6]], [[1sf7]], [[1sfb]], [[1sfg]], [[1ja2]], [[1ja4]], [[1ja6]], [[1ja7]] – HEWL + NAG oligosaccharide – Powder diffraction 
[[1ubz]], [[1d6p]], [[1d6q]], [[1bb5]] – hLys (mutant) + glycoside 
[[1uc0]], [[1re2]], [[1rem]], [[1rey]], [[1rez]], [[1lzr]], [[1lzs]] - hLys + glycoside 
[[1ljn]], [[1jef]], [[1lzy]] – tuLys + glycoside 
[[1h6m]], [[1at5]], [[1at6]], [[1lzb]], [[1lzc]], [[1lzd]], [[1lze]], [[1lzg]], [[1hew ]]– HEWL + glycoside 
[[1lsy]], [[1lsz]] - HEWL (mutant) + glycoside 
[[1bb6]], [[1bb7]] – RtLys + glycoside 
[[1lmc]] – RtLys + bulgecin 
[[1lmo]], [[1lmp]], [[1lmq]] – RtLys + glucoside 
[[1lsp]] – BsLys + bulgecin 
[[153l]], [[154l]] – Lys +glucoside – goose 

===Phage Lys===

[[2oe4]], [[2oe7]], [[2oe9]], [[2oea]], [[1swz]], [[1cx6]], [[1qtc]], [[1qtd]], [[1qth]], [[1qsb]], [[1qs5]], [[1qs9]], [[1qtb]], [[256l]], [[206l]], [[167l]], [[168l]], [[169l]], [[170l]], [[171l]], [[172l]], [[173l]], [[174l]], [[175l]], [[176l]], [[177l]], [[178l]], [[181l]], [[182l]], [[183l]], [[184l]], [[185l]], [[186l]], [[187l]], [[188l]], [[1nhb]], [[137l]], [[216l]], [[152l]], [[149l]], [[150l]], [[151l]], [[1lyd]], [[2lzm]] - T4Lys – Enterobacteria phage T4 
[[138l]] – T4Lys cross-linked 
[[4lzm]], [[5lzm]], [[6lzm]], [[7lzm]] – T4Lys ionic strength 
[[3l2x]], [[3k2r]], [[3g3v]], [[3g3w]], [[3g3x]], [[2q9d]], [[2q9e]], [[2igc]], [[2ntg]], [[2nth]], [[2ou8]], [[2ou9]], [[1zur]], [[1zwn]], [[1zyt]], [[2cuu]], [[2a4t]] – T4Lys (mutant) spin labeled 
[[3l64]], [[3hwl]], [[3jr6]], [[3gui]], [[3c7w]], [[3c7y]], [[3c7z]], [[3c80]], [[3c81]], [[3c82]], [[3c83]], [[3c8q]], [[3c8r]], [[3c8s]], [[3cdo]], [[3cdq]], [[3cdr]], [[3cdt]], [[3cdv]], [[3f8v]], [[3f9l]], [[3fa0]], [[3fad]], [[3fi5]], [[3dke]], [[3dmv]], [[2o4w]], [[2o79]], [[2o7a]], [[2huk]], [[2hul]], [[2hum]], [[2b7x]], [[2b6t]], [[2b6w]], [[2b6x]], [[2b6y]], [[2b6z]], [[2b70]], [[2b72]], [[2b73]], [[2b74]], [[2b75]], [[1sx7]], [[1swy]], [[1sx2]], [[1t6h]], [[1ssw]], [[1ssy]], [[1t8f]], [[1t8g]], [[1t8a]], [[1t97]], [[1p56]], [[1p5c]], [[1p2l]], [[1p2r]], [[1p36]], [[1p37]], [[1p3n]], [[1p46]], [[1p64]], [[1p6y]], [[1p7s]], [[1pqd]], [[1pqi]], [[1pqj]], [[1pqk]], [[1pqm]], [[1pqo]], [[1oyu]], [[1ks3]], [[1kw5]], [[1kw7]], [[1ky0]], [[1ky1]], [[1l0j]], [[1l0k]], [[1lw9]], [[1lwg]], [[1lwk]], [[1lpy]], [[1llh]], [[1lgu]], [[1li6]], [[1jtm]], [[1jtn]], [[1jqu]], [[1kni]], [[1g06]], [[1g07]], [[1g0g]], [[1g0j]], [[1g0k]], [[1g0l]], [[1g0m]], [[1g0p]], [[1g0q]], [[1g1v]], [[1g1w]], [[1i6s]], [[257l]], [[258l]], [[260l]], [[1epy]], [[1b6i]], [[1cu6]], [[1d9w]], [[1ctw]], [[1cu0]], [[1cu2]], [[1cu3]], [[1cu5]], [[1cv1]], [[1cv4]], [[1cv5]], [[1cv6]], [[1cvk]], [[1cx7]], [[1d2w]], [[1d2y]], [[1d3f]], [[1d3j]], [[1d3m]], [[1d3n]], [[1cv3]], [[1qt3]], [[1qt4]], [[1qt5]], [[1qt6]], [[1qt7]], [[1qt8]], [[1qtv]], [[1qtz]], [[1qud]], [[1qug]], [[1quh]], [[1quo]], [[1qsq]], [[261l]], [[262l]], [[259l]], [[220l]], [[222l]], [[223l]], [[225l]], [[226l]], [[227l]], [[228l]], [[229l]], [[235l]], [[236l]], [[237l]], [[238l]], [[239l]], [[240l]], [[241l]], [[242l]], [[243l]], [[244l]], [[245l]], [[246l]], [[247l]], [[248l]], [[249l]], [[250l]], [[251l]], [[252l]], [[253l]], [[254l]], [[255l]], [[230l]], [[231l]], [[232l]], [[233l]], [[234l]], [[209l]], [[210l]], [[211l]], [[212l]], [[213l]], [[214l]], [[215l]], [[218l]], [[219l]], [[180l]], [[195l]], [[196l]], [[197l]], [[198l]], [[199l]], [[200l]], [[190l]], [[191l]], [[192l]], [[189l]], [[155l]], [[156l]], [[157l]], [[158l]], [[159l]], [[160l]], [[161l]], [[162l]], [[163l]], [[164l]], [[165l]], [[166l]], [[129l]], [[130l]], [[131l]], [[140l]], [[141l]], [[142l]], [[143l]], [[144l]], [[145l]], [[146l]], [[147l]], [[201l]], [[205l]], [[221l]], [[224l]], [[102l]], [[103l]], [[104l]], [[107l]], [[108l]], [[109l]], [[110l]], [[111l]], [[112l]], [[113l]], [[114l]], [[115l]], [[118l]], [[119l]], [[120l]], [[122l]], [[123l]], [[125l]], [[126l]], [[127l]], [[128l]], [[1dya]], [[1dyb]], [[1dyc]], [[1dyd]], [[1dye]], [[1dyf]], [[1dyg]], [[1l00]], [[1l85]], [[1l86]], [[1l87]], [[1l88]], [[1l89]], [[1l90]], [[1l91]], [[1l92]], [[1l93]], [[1l94]], [[1l95]], [[1l96]], [[1l97]], [[1l98]], [[1l99]], [[1lye]], [[1lyf]], [[1lyg]], [[1lyh]], [[1lyi]], [[1lyj]], [[217l]], [[1tla]], [[1l77]], [[1l79]], [[1l80]], [[1l81]], [[1l82]], [[2l78]], [[1l36]], [[1l37]], [[1l38]], [[1l39]], [[1l40]], [[1l41]], [[1l42]], [[1l43]], [[1l44]], [[1l45]], [[1l46]], [[1l47]], [[1l48]], [[1l49]], [[1l50]], [[1l51]], [[1l52]], [[1l53]], [[1l54]], [[1l55]], [[1l56]], [[1l57]], [[1l58]], [[1l59]], [[1l60]], [[1l61]], [[1l62]], [[1l63]], [[1l64]], [[1l65]], [[1l66]], [[1l67]], [[1l68]], [[1l69]], [[1l70]], [[1l71]], [[1l72]], [[1l73]], [[1l74]], [[1l75]], [[1l76]], [[1l17]], [[1l18]], [[1l19]], [[1l20]], [[1l21]], [[1l22]], [[1l23]], [[1l24]], [[1l25]], [[1l26]], [[1l27]], [[1l28]], [[1l29]], [[1l30]], [[1l31]], [[1l32]], [[1l33]], [[1l34]], [[1l35]], [[3lzm]], [[1l01]], [[1l02]], [[1l03]], [[1l04]], [[1l05]], [[1l06]], [[1l07]], [[1l08]], [[1l09]], [[1l10]], [[1l11]], [[1l12]], [[1l13]], [[1l14]], [[1l15]], [[1l16]] – T4Lys (mutant) 
[[1c60]], [[1c61]], [[1c62]], [[1c63]], [[1c64]], [[1c65]], [[1c66]], [[1c67]], [[1c68]], [[1c69]], [[1c6a]], [[1c6b]], [[1c6c]], [[1c6d]], [[1c6e]], [[1c6f]], [[1c6g]], [[1c6h]], [[1c6i]], [[1c6j]], [[1c6k]], [[1c6l]], [[1c6m]], [[1c6n]], [[1c6p]], [[1c6q]], [[1c6t]] - T4Lys (mutant) + noble gas 
[[3ht6]], [[3ht7]], [[3ht8]], [[3ht9]], [[3htb]], [[3hu8]], [[3huq]], [[3guj]], [[3guk]], [[3gul]], [[3gum]], [[3gun]], [[3guo]], [[3gup]], [[3dmx]], [[3dmz]], [[3dn0]], [[3dn1]], [[3dn2]], [[3dn3]], [[3dn4]], [[3dn6]], [[3dn8]], [[3dna]], [[2rb1]], [[2ray]], [[2raz]], [[2rb0]], [[2rb2]], [[2rbn]], [[2rbo]], [[2rbq]], [[2rbr]], [[2rbs]], [[2oty]],[[2otz]], [[1owy]], [[1owz]], [[1ov5]], [[1ov7]], [[1ovh]], [[1ovj]], [[1ovk]], [[1lgw]], [[1lgx]], [[1li2]], [[1li3]], [[1l83]], [[1l84]] – T4Lys (mutant) + benzene derivative 
[[3htd]], [[3htf]], [[3htg]], [[3hu9]], [[3hua]], [[3huk]], [[3hh3]], [[3hh4]], [[3hh5]], [[3hh6]], [[2rbp]], [[2ou0]], [[2f2q]], [[2f32]], [[2f47]], [[1xep]] – T4Lys (mutant) + inhibitor 
[[148l]] - T4Lys (mutant) + glucoside 
[[3d3d]], [[1d9u]] – lamLys + chitohexasaccharide 
[[1am7]] – lamLys - Enterobacteria phage λ 
[[2anv]], [[2anx]] – Lys (mutant)]] - Enterobacteria phage p22 
[[1xjt]], [[1xju]] - Lys - Enterobacteria phage p1 
[[1lba]] - T7Lys - Enterobacteria phage T7 

===Lys protein complex===

[[3m18]], [[3g3a]], [[3g3b]] - HEWL + Variable lymphocyte receptor – Marine lamprey 
[[3a67]], [[3a6b]], [[3a6c]], [[2yss]], [[2eiz]], [[2dqc]], [[2dqd]], [[2dqe]], [[2dqf]], [[2dqg]], [[2dqh]], [[2dqi]], [[2dqj]], [[1j1o]], [[1j1p]], [[1j1x]], [[1ic4]], [[1ic5]], [[1ic7]] – HEWL + mLys antibody HYHEL-10 (mutant) 
[[1xgp]], [[1xgq]], [[1xgr]], [[1xgt]], [[1xgu]] – HEWL + mLys antibody HYHEL-63 
[[3d9a]], [[2eks]], [[1ua6]], [[1c08]], [[3hfm]] – HEWL + mLys antibody HYHEL-10 
[[1uac]] - tuLys C + mLys antibody HYHEL-10 
[[1yqv]], [[2iff]] – HEWL + mLys antibody HYHEL-5 
[[1bql]] – BqLys + mLys antibody HYHEL-5 
[[1ndg]] – HEWL + mLys antibody HYHEL-8 
[[1ndm]] – HEWL + mLys antibody HYHEL-26 
[[1dqj]] - HEWL + mLys antibody HYHEL-63 
[[1nby]], [[1nbz]] – HEWL (mutant) + mLys antibody HYHEL-63 
[[1g7h]], [[1g7i]], [[1g7j]], [[1g7l]], [[1g7m]], [[1kip]], [[1kiq]], [[1kir]] – HEWL + mAnti-HEWL monoclonal antibody (mutant) 
[[1mlc]], [[1vfb]] - HEWL + mIGG1-κ D44.1 FAB 
[[1a2y]] - HEWL (mutant) + mIGG1-κ D1.3 FV 
[[1fdl]] - HEWL + mIGG1-κ D1.3 FAB 
[[1jhl]] – phLys + mIGG1-κ D11.15 FV 
[[1fbi]] – GfLys + mIGG1 F9.13.7 FAB 
[[2znw]], [[2znx]] – HEWL + hSCFV10 antibody 
[[1bvk]] - HEWL + hAnti Lys FV antibody 
[[1dzb]] – tuLys + mSCFV 1F9 
[[1zv5]], [[1zvh]], [[1zvy]], [[1zmy]], [[1ri8]], [[1rjc]], [[1xfp]], [[1jtp]], [[1jtt]], [[1jto]], [[1mel]] - HEWL + cAntibody heavy chain domain – camel 
[[1op9]] - hLys C + cAntibody heavy chain domain 
[[3otp]] – HEWL + EcProtease DO – ''Escherichia coli'' 
[[3f6z]] - HEWL + MLIC – ''Pseudomonas aeruginosa'' 
[[3eba]] – hLys C + hCABHUL6 
[[2qb0]], [[2qar]] – T4Lys/E80 TELSAM domain 
[[2i25]], [[2i26]] - HEWL +NsAntigen receptor PBLA8 variable domain – Nurse shark 
[[1sq2]], [[1t6v]] – HEWL +NsNew Antigen receptor variable domain 
[[1gpq]] – HEWL + EcInhibitor of Vertebrate Lys 
[[1aro]] – T7Lys + T7 RNA polymerase 

===Some Useful External Links===
[http://en.wikipedia.org/wiki/Lysozyme Lysozyme]

[http://en.wikipedia.org/wiki/Glycoside_hydrolase#Retaining_glycoside_hydrolases Retaining Glycoside Hydrolases]

===References===
<references/>

Hen Egg-White (HEW) Lysozyme

2011-03-31T01:19:04Z

Anne Goodling:

<applet load='aln_1H6M_to_1HEW_2.pdb' size='300' frame='true' align='right' caption=' Hen Egg White (HEW) Lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to the active site, PDBid 1HEW' scene='User:Judy_Voet/Lysozyme/Lysozyme1/16' />
Lysozyme was the first enzyme whose X-ray structure was determined <ref> PMID 5840126</ref><ref>Phillips, D. C. The hen egg white lysozyme molecule. Proc. Natl Acad. Sci. USA 57, 483-495 (1967)</ref>. This <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>scene </scene> shows Hen Egg White (HEW) lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to a cleft in the enzyme. David Phillips, who determined the structure in 1965, saw that the cleft was large enough to fit three more saccharide units.
He therefore built a model extending the trisaccharide to a
<scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> that fits into the cleft, labeling the sugar subsites A-F<ref> coordinates of the model kindly provided by Louise Johnson</ref>. Alternately click on <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>trisaccharide</scene> and <scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> to turn the modeled portion of the hexasaccharide on and off.

<applet load='aln_1H6M_to_1HEW_2.pdb' size='300' frame='true' align='left' caption='NAG-2-deoxy-2-fluoro-glucosyl fluoride (NAG2FGlcF) bound to Glu35Gln HEW Lysozyme PDBid 1H6M' scene='User:Judy_Voet/Lysozyme/1h6m/3'/>
The interesting thing about the model was that the only way that the hexasaccharide would fit into the cleft was if the 4th saccharide (in subsite D) was strained into a <scene name='User:Judy_Voet/Lysozyme/Half-chair/2'>half-chair conformation</scene>. This conformation is what would be necessary for the formation of an oxocarbenium ion (oxionium ion). When the model was studied, <scene name='User:Judy_Voet/Lysozyme/Glu_35/1'>Glu 35</scene> was found to be in an ideal location to act as a general acid catalyst, 3.34 Angstroms from the bridging oxygen between the 4th and 5th saccharide units. <scene name='User:Judy_Voet/Lysozyme/Asp_52/2'>Asp 52</scene> appeared to be too far away (2.69 angstroms) in the static lysozyme structure to have formed a covalent bond with C1 of the half-chair model in the D site, and no covalent intermediate had ever been detected, so Phillips proposed that it acted as an electrostatic stabilizer of the oxonium ion (referred to as The Phillips Mechanism).

Then, in 2001, Stephen Withers published <scene name='User:Judy_Voet/Lysozyme/1h6m/3'>1H6M</scene>,<ref>PMID 11518970</ref> in which Glu 35 had been mutated to Gln to remove the general acid catalyst. The substrate contained NAG-2-fluoro-glucosyl fluoride (NAG2FGlcF). The fluoro group on C-1 does not require acid catalysis to be a good leaving group, and the remaining saccharide, in the absence of the acid necessary to catalyse the second step of the reaction, was demonstrated to form a <scene name='User:Judy_Voet/Lysozyme/Covalent/1'> covalent intermediate</scene>. In this <scene name='User:Judy_Voet/Lysozyme/Superposition/2'>superposition</scene> of the half chair model with 1HEW (greens) and the covalent intermediate in 1H6M (blues), note the relatively small motions of Asp 52 and C1 of the sugar ring in going from the model to the covalent intermediate. to observe the motion from the <scene name='User:Judy_Voet/Lysozyme/Asp52_halfchair/1'>half-chair</scene> to the <scene name='User:Judy_Voet/Lysozyme/Covalent/2'>covalent intermediate</scene> just toggle between the two green links.

== 3D Structures of Lysozyme ==

===Lys===

[[2x0a]], [[3iju]], [[3ijv]], [[3a8z]], [[2w1y]], [[2w1m]], [[2w1x]], [[2w1l]], [[3e3d]], [[3exd]], [[2zq3]], [[2zq4]], [[3b72]], [[3b6l]], [[2z12]], [[2z18]], [[2z19]], [[2vb1]], [[2hu3]], [[2hub]], [[2htx]], [[2hu1]], [[2yvb]], [[2epe]], [[2g4p]], [[2g4q]], [[2cgi]], [[2b5z]], [[2d4k]], [[2d91]], [[2f2n]], [[2fbb]], [[2c8o]], [[2c8p]], [[2a6u]], [[2aub]], [[2blx]], [[2bly]], [[2a7d]], [[2a7f]], [[1wtm]], [[1wtn]], [[1w6z]], [[1vdp]], [[1vdq]], [[1vds]], [[1vdt]], [[1ved]], [[1v7t]], [[1ps5]], [[2cds]], [[1lj3]], [[1lj4]], [[1lje]], [[1ljf]], [[1ljg]], [[1ljh]], [[1lji]], [[1ljj]], [[1ljk]], [[1jis]], [[1jit]], [[1jiy]], [[1jj0]], [[1jj1]], [[1jj3]], [[1iee]], [[1qio]], [[1f0w]], [[1f10]], [[1dpx]], [[1c10]], [[1qtk]], [[1lz8]], [[1lz9]], [[1bhz]], [[1bgi]], [[1bwh]], [[1bwi]], [[1bwj]], [[1bvx]], [[1hsw]], [[1hsx]], [[1lpi]], [[4lzt]], [[3lzt]], [[1aki]], [[1jpo]], [[1rfp]], [[193l]], [[194l]], [[5lym]], [[1lza]], [[3lyt]], [[4lyt]], [[5lyt]], [[6lyt]], [[2lzt]], [[1lzt]], [[1lzh]], [[2lzh]], [[7lyz]], [[1lyz]], [[2lyz]], [[3lyz]], [[4lyz]], [[5lyz]], [[6lyz]] - HEWL – chicken 
[[1xei]], [[1xej]], [[1xek]], [[1uco]], [[1lma]], [[4lym]] – HEWL low hydration 
[[1lsa]], [[1lsb]], [[1lsc]], [[1lsd]], [[1lse]], [[1lsf]], [[1lys]] – HEWL temperature influence 
[[2lym]], [[3lym]] – HEWL pressure influence 
[[132l]] – HEWL methylated 
[[1rcm]] – HEWL 3 S-S form 
[[2xbr]], [[2xbs]]- HEWL– Raman crystallography 
[[2zwb]], [[1io5]], [[1lzn]] - HEWL– Neutron 
[[1gxv]], [[1gxx]], [[1e8l]] - HEWL- NMR 
[[2hs7]], [[2hso]], [[2hs9]]- HEWL– Powder diffraction 
[[1ir7]], [[1ir8]], [[1ir9]], [[1ioq]], [[1ior]], [[1ios]], [[1iot]], [[1flq]], [[1flu]], [[1flw]], [[1fly]], [[1fn5]], [[1kxw]], [[1kxx]], [[1kxy]], [[1uia]], [[1uib]], [[1uic]], [[1uid]], [[1uie]], [[1uif]], [[1uig]], [[1uih]], [[1lsm]], [[1lsn]], [[1hel]], [[1hem]], [[1hen]], [[1heo]], [[1hep]], [[1heq]], [[1her]] – HEWL (mutant) 
[[1lyo]], [[2lyo]], [[3lyo]], [[4lyo]] – HEWL cross-linked 
[[1xft]] - tuLys – turkey - Powder diffraction 
[[1jse]], [[1tew]], [[135l]], [[2lz2]], [[1lz2]] – tuLys 
[[3lz2]] – tuLys - Laue 
[[3ab6]] – Lys + NAG3 – Hard clam 
[[2x8r]] – Lys GH25 – ''Aspergillus fumigatus'' 
[[3mgw]] – Lys G – Atlantic salmon 
[[3gxk]], [[3gxr]] – Lys G + NAG – Atlantic cod 
[[2fbd]] – HfLys 1 
[[3cb7]] – HfLys 2 
[[2zij]], [[2zik]], [[2zil]], [[2nwd]], [[1iwt]], [[1iwu]], [[1iwv]], [[1iww]], [[1iwx]], [[1iwy]], [[1iwz]], [[1jwr]], [[1jsf]], [[1rex]], [[1lz1]] – hLys – human 
[[1w08]], [[1ix0]], [[1ioc]], [[1ip1]], [[1ip2]], [[1ip3]], [[1ip4]], [[1ip5]], [[1ip6]], [[1ip7]], [[1qsw]], [[1gev]], [[1gez]], [[1gf0]], [[1gf3]], [[1gf4]], [[1gf5]], [[1gf6]], [[1gf7]], [[1i1z]], [[1i20]], [[1i22]], [[1gfr]], [[1gft]], [[1gfu]], [[1gfv]], [[1gf8]], [[1gf9]], [[1gfa]], [[1gfe]], [[1gfg]], [[1gfh]], [[1gfj]], [[1gfk]], [[1inu]], [[1gdx]], [[1ge0]], [[1ge1]], [[1ge2]], [[1ge3]], [[1ge4]], [[1gdw]], [[1gaz]], [[1gb0]], [[1gb2]], [[1gb3]], [[1gb5]], [[1gb6]], [[1gb7]], [[1gb8]], [[1gb9]], [[1gbo]], [[1gbw]], [[1gbx]], [[1gby]], [[1gbz]], [[1gay]], [[1eq4]], [[1eq5]], [[1eqe]], [[1c7p]], [[1di3]], [[1di4]], [[1di5]], [[1c43]], [[1c45]], [[1c46]], [[1ckg]], [[1cj6]], [[1cj7]], [[1cj8]], [[1cj9]], [[1ckc]], [[1ckd]], [[1ckf]], [[1ckh]], [[1b5z]], [[1b70]], [[1b7q]], [[1b7r]], [[1b7s]], [[1b7l]], [[1b7m]], [[1b7n]], [[1b7p]], [[1b5u]], [[1b5v]], [[1b5w]], [[1b5x]], [[1b5y]], [[1bb3]], [[1bb4]], [[2bqa]], [[2bqb]], [[2bqc]], [[2bqd]], [[2bqe]], [[2bqf]], [[2bqg]], [[2bqh]], [[2bqi]], [[2bqj]], [[2bqk]], [[2bql]], [[2bqm]], [[2bqn]], [[2bqo]], [[2mea]], [[2meb]], [[2mec]], [[2med]], [[2mee]], [[2mef]], [[2meg]], [[2meh]], [[2mei]], [[1wqm]], [[1wqn]], [[1wqo]], [[1wqp]], [[1wqq]], [[1wqr]], [[2heb]], [[2hea]], [[2hec]], [[2hed]], [[2hee]], [[2hef]], [[1jka]], [[1jkb]], [[1jkc]], [[1jkd]], [[1loz]], [[1lyy]], [[1oua]], [[1oub]], [[1ouc]], [[1oud]], [[1oue]], [[1ouf]], [[1oug]], [[1ouh]], [[1oui]], [[1ouj]], [[207l]], [[208l ]], [[1yam]], [[1yan]], [[1yao]], [[1yap]], [[1yaq]], [[1lmt]], [[1lhh]], [[1lhi]], [[1lhj]], [[1lhk]], [[1lhl]], [[133l]], [[134l]], [[1lz4]], [[1lz5]], [[1lz6]], [[1laa]], [[1tay]], [[1tby]], [[1tcy]], [[1tdy]], [[2lhm]], [[3lhm]] – hLys (mutant) 
[[1iy3]], [[1iy4]] – hLys - NMR 
[[2z2f]] – Lys – Bovine 
[[2cwi]], [[1el1]], [[1qqy]] – dLys - dog 
[[2z2e]] – dLys (mutant) 
[[1i56]] – dLys – NMR 
[[2dqa]] – Lys – ''Tapes japonica'' 
[[2gv0]] – Lys – Soft-shelled turtle 
[[1ivm]] – mLys M – NMR – mouse 
[[1jfx]] – Lys – ''Streptomyces coelicolor'' 
[[1gd6]] – Lys – ''Bombyx mori'' 
[[1jug]] – Lys – Echidna 
[[1dkj]] – BqLys – Bobwhite quail 
[[2ihl]] – Lys – Japanese quail 
[[1gbs]] – BsLys – Black swan 
[[1lmn]] – RtLys – Rainbow trout 
[[2eql]] – Lys – horse 
[[1ghl]] – phLys – pheasant 
[[1hhl]] – GfLys – Guinea fowl 
[[1lhm]] – Lys (mutant) – yeast 

===Lys small molecules complexes===

[[3fe0]], [[2d4i]], [[2d4j]], [[1v7s]] - HEWL+ D2O 
[[3m3u]] – HEWL Trp fluorescence 
[[2xjw]] - HEWL + CO 
[[1hf4]], [[1lks]] – HEWL + NO3 
[[3a34]], [[3ems]] - HEWL + arginine 
[[2xth]] – cLys + inhibitor K2PtBr6 
[[3a90]], [[3a91]], [[3a92]], [[3a93]], [[3a94]], [[3a95]], [[3a96]], [[3kam]], [[2pc2]], [[2bpu]], [[1t3p]], [[1h87]] – HEWL + rare earth 
[[2d6b]], [[2hg0]], [[1vat]], [[1gwd]], [[1b2k]], [[1lkr]], [[1azf]], [[8lyz]]- HEWL+ halogen 
[[1vat]] - HEWL + Xe 
[[1n4f]] - HEWL + As 
[[2i6z]] - HEWL + Pt drug 
[[2zyp]] - HEWL + poly (allyl amine) 
[[2f30]], [[2f4a]] – HEWL + urea derivative 
[[2f4g]], [[1ykx]], [[1yky]], [[1ykz]], [[1yl0]], [[1yl1]], [[1z55]] - HEWL + alcohol 
[[1dpw]] – HEWL + MPD 
[[1lcn]] – HEWL + SCN 
[[2zxs]] - HEWL with glycine-amide 
[[2h9j]], [[2h9k]], [[1yik]], [[1yil]] - HEWL + cyclam derivative 
[[1b0d]] – HEWL + p-toluene-sulfonate 
[[2q0m]] - HEWL + tricarbonylmanganese 
[[2war]] – HEWL (mutant) + chitopentaose 
[[2h5z]] – HfLys 1 + chitotetraose – House fly 
[[1hnl]] – hLys + glutathione 
[[1dkk]] – BqLys + NO3 

===Lys complex with glucoside===

[[3a3q]] – HEWL (mutant) + NAG 
[[1sf4]], [[1sf6]], [[1sf7]], [[1sfb]], [[1sfg]], [[1ja2]], [[1ja4]], [[1ja6]], [[1ja7]] – HEWL + NAG oligosaccharide – Powder diffraction 
[[1ubz]], [[1d6p]], [[1d6q]], [[1bb5]] – hLys (mutant) + glycoside 
[[1uc0]], [[1re2]], [[1rem]], [[1rey]], [[1rez]], [[1lzr]], [[1lzs]] - hLys + glycoside 
[[1ljn]], [[1jef]], [[1lzy]] – tuLys + glycoside 
[[1h6m]], [[1at5]], [[1at6]], [[1lzb]], [[1lzc]], [[1lzd]], [[1lze]], [[1lzg]], [[1hew ]]– HEWL + glycoside 
[[1lsy]], [[1lsz]] - HEWL (mutant) + glycoside 
[[1bb6]], [[1bb7]] – RtLys + glycoside 
[[1lmc]] – RtLys + bulgecin 
[[1lmo]], [[1lmp]], [[1lmq]] – RtLys + glucoside 
[[1lsp]] – BsLys + bulgecin 
[[153l]], [[154l]] – Lys +glucoside – goose 

===Phage Lys===

[[2oe4]], [[2oe7]], [[2oe9]], [[2oea]], [[1swz]], [[1cx6]], [[1qtc]], [[1qtd]], [[1qth]], [[1qsb]], [[1qs5]], [[1qs9]], [[1qtb]], [[256l]], [[206l]], [[167l]], [[168l]], [[169l]], [[170l]], [[171l]], [[172l]], [[173l]], [[174l]], [[175l]], [[176l]], [[177l]], [[178l]], [[181l]], [[182l]], [[183l]], [[184l]], [[185l]], [[186l]], [[187l]], [[188l]], [[1nhb]], [[137l]], [[216l]], [[152l]], [[149l]], [[150l]], [[151l]], [[1lyd]], [[2lzm]] - T4Lys – Enterobacteria phage T4 
[[138l]] – T4Lys cross-linked 
[[4lzm]], [[5lzm]], [[6lzm]], [[7lzm]] – T4Lys ionic strength 
[[3l2x]], [[3k2r]], [[3g3v]], [[3g3w]], [[3g3x]], [[2q9d]], [[2q9e]], [[2igc]], [[2ntg]], [[2nth]], [[2ou8]], [[2ou9]], [[1zur]], [[1zwn]], [[1zyt]], [[2cuu]], [[2a4t]] – T4Lys (mutant) spin labeled 
[[3l64]], [[3hwl]], [[3jr6]], [[3gui]], [[3c7w]], [[3c7y]], [[3c7z]], [[3c80]], [[3c81]], [[3c82]], [[3c83]], [[3c8q]], [[3c8r]], [[3c8s]], [[3cdo]], [[3cdq]], [[3cdr]], [[3cdt]], [[3cdv]], [[3f8v]], [[3f9l]], [[3fa0]], [[3fad]], [[3fi5]], [[3dke]], [[3dmv]], [[2o4w]], [[2o79]], [[2o7a]], [[2huk]], [[2hul]], [[2hum]], [[2b7x]], [[2b6t]], [[2b6w]], [[2b6x]], [[2b6y]], [[2b6z]], [[2b70]], [[2b72]], [[2b73]], [[2b74]], [[2b75]], [[1sx7]], [[1swy]], [[1sx2]], [[1t6h]], [[1ssw]], [[1ssy]], [[1t8f]], [[1t8g]], [[1t8a]], [[1t97]], [[1p56]], [[1p5c]], [[1p2l]], [[1p2r]], [[1p36]], [[1p37]], [[1p3n]], [[1p46]], [[1p64]], [[1p6y]], [[1p7s]], [[1pqd]], [[1pqi]], [[1pqj]], [[1pqk]], [[1pqm]], [[1pqo]], [[1oyu]], [[1ks3]], [[1kw5]], [[1kw7]], [[1ky0]], [[1ky1]], [[1l0j]], [[1l0k]], [[1lw9]], [[1lwg]], [[1lwk]], [[1lpy]], [[1llh]], [[1lgu]], [[1li6]], [[1jtm]], [[1jtn]], [[1jqu]], [[1kni]], [[1g06]], [[1g07]], [[1g0g]], [[1g0j]], [[1g0k]], [[1g0l]], [[1g0m]], [[1g0p]], [[1g0q]], [[1g1v]], [[1g1w]], [[1i6s]], [[257l]], [[258l]], [[260l]], [[1epy]], [[1b6i]], [[1cu6]], [[1d9w]], [[1ctw]], [[1cu0]], [[1cu2]], [[1cu3]], [[1cu5]], [[1cv1]], [[1cv4]], [[1cv5]], [[1cv6]], [[1cvk]], [[1cx7]], [[1d2w]], [[1d2y]], [[1d3f]], [[1d3j]], [[1d3m]], [[1d3n]], [[1cv3]], [[1qt3]], [[1qt4]], [[1qt5]], [[1qt6]], [[1qt7]], [[1qt8]], [[1qtv]], [[1qtz]], [[1qud]], [[1qug]], [[1quh]], [[1quo]], [[1qsq]], [[261l]], [[262l]], [[259l]], [[220l]], [[222l]], [[223l]], [[225l]], [[226l]], [[227l]], [[228l]], [[229l]], [[235l]], [[236l]], [[237l]], [[238l]], [[239l]], [[240l]], [[241l]], [[242l]], [[243l]], [[244l]], [[245l]], [[246l]], [[247l]], [[248l]], [[249l]], [[250l]], [[251l]], [[252l]], [[253l]], [[254l]], [[255l]], [[230l]], [[231l]], [[232l]], [[233l]], [[234l]], [[209l]], [[210l]], [[211l]], [[212l]], [[213l]], [[214l]], [[215l]], [[218l]], [[219l]], [[180l]], [[195l]], [[196l]], [[197l]], [[198l]], [[199l]], [[200l]], [[190l]], [[191l]], [[192l]], [[189l]], [[155l]], [[156l]], [[157l]], [[158l]], [[159l]], [[160l]], [[161l]], [[162l]], [[163l]], [[164l]], [[165l]], [[166l]], [[129l]], [[130l]], [[131l]], [[140l]], [[141l]], [[142l]], [[143l]], [[144l]], [[145l]], [[146l]], [[147l]], [[201l]], [[205l]], [[221l]], [[224l]], [[102l]], [[103l]], [[104l]], [[107l]], [[108l]], [[109l]], [[110l]], [[111l]], [[112l]], [[113l]], [[114l]], [[115l]], [[118l]], [[119l]], [[120l]], [[122l]], [[123l]], [[125l]], [[126l]], [[127l]], [[128l]], [[1dya]], [[1dyb]], [[1dyc]], [[1dyd]], [[1dye]], [[1dyf]], [[1dyg]], [[1l00]], [[1l85]], [[1l86]], [[1l87]], [[1l88]], [[1l89]], [[1l90]], [[1l91]], [[1l92]], [[1l93]], [[1l94]], [[1l95]], [[1l96]], [[1l97]], [[1l98]], [[1l99]], [[1lye]], [[1lyf]], [[1lyg]], [[1lyh]], [[1lyi]], [[1lyj]], [[217l]], [[1tla]], [[1l77]], [[1l79]], [[1l80]], [[1l81]], [[1l82]], [[2l78]], [[1l36]], [[1l37]], [[1l38]], [[1l39]], [[1l40]], [[1l41]], [[1l42]], [[1l43]], [[1l44]], [[1l45]], [[1l46]], [[1l47]], [[1l48]], [[1l49]], [[1l50]], [[1l51]], [[1l52]], [[1l53]], [[1l54]], [[1l55]], [[1l56]], [[1l57]], [[1l58]], [[1l59]], [[1l60]], [[1l61]], [[1l62]], [[1l63]], [[1l64]], [[1l65]], [[1l66]], [[1l67]], [[1l68]], [[1l69]], [[1l70]], [[1l71]], [[1l72]], [[1l73]], [[1l74]], [[1l75]], [[1l76]], [[1l17]], [[1l18]], [[1l19]], [[1l20]], [[1l21]], [[1l22]], [[1l23]], [[1l24]], [[1l25]], [[1l26]], [[1l27]], [[1l28]], [[1l29]], [[1l30]], [[1l31]], [[1l32]], [[1l33]], [[1l34]], [[1l35]], [[3lzm]], [[1l01]], [[1l02]], [[1l03]], [[1l04]], [[1l05]], [[1l06]], [[1l07]], [[1l08]], [[1l09]], [[1l10]], [[1l11]], [[1l12]], [[1l13]], [[1l14]], [[1l15]], [[1l16]] – T4Lys (mutant) 
[[1c60]], [[1c61]], [[1c62]], [[1c63]], [[1c64]], [[1c65]], [[1c66]], [[1c67]], [[1c68]], [[1c69]], [[1c6a]], [[1c6b]], [[1c6c]], [[1c6d]], [[1c6e]], [[1c6f]], [[1c6g]], [[1c6h]], [[1c6i]], [[1c6j]], [[1c6k]], [[1c6l]], [[1c6m]], [[1c6n]], [[1c6p]], [[1c6q]], [[1c6t]] - T4Lys (mutant) + noble gas 
[[3ht6]], [[3ht7]], [[3ht8]], [[3ht9]], [[3htb]], [[3hu8]], [[3huq]], [[3guj]], [[3guk]], [[3gul]], [[3gum]], [[3gun]], [[3guo]], [[3gup]], [[3dmx]], [[3dmz]], [[3dn0]], [[3dn1]], [[3dn2]], [[3dn3]], [[3dn4]], [[3dn6]], [[3dn8]], [[3dna]], [[2rb1]], [[2ray]], [[2raz]], [[2rb0]], [[2rb2]], [[2rbn]], [[2rbo]], [[2rbq]], [[2rbr]], [[2rbs]], [[2oty]],[[2otz]], [[1owy]], [[1owz]], [[1ov5]], [[1ov7]], [[1ovh]], [[1ovj]], [[1ovk]], [[1lgw]], [[1lgx]], [[1li2]], [[1li3]], [[1l83]], [[1l84]] – T4Lys (mutant) + benzene derivative 
[[3htd]], [[3htf]], [[3htg]], [[3hu9]], [[3hua]], [[3huk]], [[3hh3]], [[3hh4]], [[3hh5]], [[3hh6]], [[2rbp]], [[2ou0]], [[2f2q]], [[2f32]], [[2f47]], [[1xep]] – T4Lys (mutant) + inhibitor 
[[148l]] - T4Lys (mutant) + glucoside 
[[3d3d]], [[1d9u]] – lamLys + chitohexasaccharide 
[[1am7]] – lamLys - Enterobacteria phage λ 
[[2anv]], [[2anx]] – Lys (mutant)]] - Enterobacteria phage p22 
[[1xjt]], [[1xju]] - Lys - Enterobacteria phage p1 
[[1lba]] - T7Lys - Enterobacteria phage T7 

===Lys protein complex===

[[3m18]], [[3g3a]], [[3g3b]] - HEWL + Variable lymphocyte receptor – Marine lamprey 
[[3a67]], [[3a6b]], [[3a6c]], [[2yss]], [[2eiz]], [[2dqc]], [[2dqd]], [[2dqe]], [[2dqf]], [[2dqg]], [[2dqh]], [[2dqi]], [[2dqj]], [[1j1o]], [[1j1p]], [[1j1x]], [[1ic4]], [[1ic5]], [[1ic7]] – HEWL + mLys antibody HYHEL-10 (mutant) 
[[1xgp]], [[1xgq]], [[1xgr]], [[1xgt]], [[1xgu]] – HEWL + mLys antibody HYHEL-63 
[[3d9a]], [[2eks]], [[1ua6]], [[1c08]], [[3hfm]] – HEWL + mLys antibody HYHEL-10 
[[1uac]] - tuLys C + mLys antibody HYHEL-10 
[[1yqv]], [[2iff]] – HEWL + mLys antibody HYHEL-5 
[[1bql]] – BqLys + mLys antibody HYHEL-5 
[[1ndg]] – HEWL + mLys antibody HYHEL-8 
[[1ndm]] – HEWL + mLys antibody HYHEL-26 
[[1dqj]] - HEWL + mLys antibody HYHEL-63 
[[1nby]], [[1nbz]] – HEWL (mutant) + mLys antibody HYHEL-63 
[[1g7h]], [[1g7i]], [[1g7j]], [[1g7l]], [[1g7m]], [[1kip]], [[1kiq]], [[1kir]] – HEWL + mAnti-HEWL monoclonal antibody (mutant) 
[[1mlc]], [[1vfb]] - HEWL + mIGG1-κ D44.1 FAB 
[[1a2y]] - HEWL (mutant) + mIGG1-κ D1.3 FV 
[[1fdl]] - HEWL + mIGG1-κ D1.3 FAB 
[[1jhl]] – phLys + mIGG1-κ D11.15 FV 
[[1fbi]] – GfLys + mIGG1 F9.13.7 FAB 
[[2znw]], [[2znx]] – HEWL + hSCFV10 antibody 
[[1bvk]] - HEWL + hAnti Lys FV antibody 
[[1dzb]] – tuLys + mSCFV 1F9 
[[1zv5]], [[1zvh]], [[1zvy]], [[1zmy]], [[1ri8]], [[1rjc]], [[1xfp]], [[1jtp]], [[1jtt]], [[1jto]], [[1mel]] - HEWL + cAntibody heavy chain domain – camel 
[[1op9]] - hLys C + cAntibody heavy chain domain 
[[3otp]] – HEWL + EcProtease DO – ''Escherichia coli'' 
[[3f6z]] - HEWL + MLIC – ''Pseudomonas aeruginosa'' 
[[3eba]] – hLys C + hCABHUL6 
[[2qb0]], [[2qar]] – T4Lys/E80 TELSAM domain 
[[2i25]], [[2i26]] - HEWL +NsAntigen receptor PBLA8 variable domain – Nurse shark 
[[1sq2]], [[1t6v]] – HEWL +NsNew Antigen receptor variable domain 
[[1gpq]] – HEWL + EcInhibitor of Vertebrate Lys 
[[1aro]] – T7Lys + T7 RNA polymerase 

===Some Useful External Links===
[http://en.wikipedia.org/wiki/Lysozyme Lysozyme]

[http://en.wikipedia.org/wiki/Glycoside_hydrolase#Retaining_glycoside_hydrolases Retaining Glycoside Hydrolases]

===References===
<references/>

Hen Egg-White (HEW) Lysozyme

2011-03-31T01:17:21Z

Anne Goodling:

<applet load='aln_1H6M_to_1HEW_2.pdb' size='300' frame='true' align='right' caption=' Hen Egg White (HEW) Lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to the active site, PDBid 1HEW' scene='User:Judy_Voet/Lysozyme/Lysozyme1/16' />
Lysozyme was the first enzyme whose X-ray structure was determined <ref> PMID 5840126</ref><ref>Phillips, D. C. The hen egg white lysozyme molecule. Proc. Natl Acad. Sci. USA 57, 483-495 (1967)</ref>. This <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>scene </scene> shows Hen Egg White (HEW) lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to a cleft in the enzyme. David Phillips, who determined the structure in 1965, saw that the cleft was large enough to fit three more saccharide units.
He therefore built a model extending the trisaccharide to a
<scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> that fits into the cleft, labeling the sugar subsites A-F<ref> coordinates of the model kindly provided by Louise Johnson</ref>. Alternately click on <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>trisaccharide</scene> and <scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> to turn the modeled portion of the hexasaccharide on and off.

The interesting thing about the model was that the only way that the hexasaccharide would fit into the cleft was if the 4th saccharide (in subsite D) was strained into a <scene name='User:Judy_Voet/Lysozyme/Half-chair/2'>half-chair conformation</scene>. This conformation is what would be necessary for the formation of an oxocarbenium ion (oxionium ion). When the model was studied, <scene name='User:Judy_Voet/Lysozyme/Glu_35/1'>Glu 35</scene> was found to be in an ideal location to act as a general acid catalyst, 3.34 Angstroms from the bridging oxygen between the 4th and 5th saccharide units. <scene name='User:Judy_Voet/Lysozyme/Asp_52/2'>Asp 52</scene> appeared to be too far away (2.69 angstroms) in the static lysozyme structure to have formed a covalent bond with C1 of the half-chair model in the D site, and no covalent intermediate had ever been detected, so Phillips proposed that it acted as an electrostatic stabilizer of the oxonium ion (referred to as The Phillips Mechanism).
<applet load='aln_1H6M_to_1HEW_2.pdb' size='300' frame='true' align='left' caption='NAG-2-deoxy-2-fluoro-glucosyl fluoride (NAG2FGlcF) bound to Glu35Gln HEW Lysozyme PDBid 1H6M' scene='User:Judy_Voet/Lysozyme/1h6m/3'/>

Then, in 2001, Stephen Withers published <scene name='User:Judy_Voet/Lysozyme/1h6m/3'>1H6M</scene>,<ref>PMID 11518970</ref> in which Glu 35 had been mutated to Gln to remove the general acid catalyst. The substrate contained NAG-2-fluoro-glucosyl fluoride (NAG2FGlcF). The fluoro group on C-1 does not require acid catalysis to be a good leaving group, and the remaining saccharide, in the absence of the acid necessary to catalyse the second step of the reaction, was demonstrated to form a <scene name='User:Judy_Voet/Lysozyme/Covalent/1'> covalent intermediate</scene>. In this <scene name='User:Judy_Voet/Lysozyme/Superposition/2'>superposition</scene> of the half chair model with 1HEW (greens) and the covalent intermediate in 1H6M (blues), note the relatively small motions of Asp 52 and C1 of the sugar ring in going from the model to the covalent intermediate. to observe the motion from the <scene name='User:Judy_Voet/Lysozyme/Asp52_halfchair/1'>half-chair</scene> to the <scene name='User:Judy_Voet/Lysozyme/Covalent/2'>covalent intermediate</scene> just toggle between the two green links.

== 3D Structures of Lysozyme ==

===Lys===

[[2x0a]], [[3iju]], [[3ijv]], [[3a8z]], [[2w1y]], [[2w1m]], [[2w1x]], [[2w1l]], [[3e3d]], [[3exd]], [[2zq3]], [[2zq4]], [[3b72]], [[3b6l]], [[2z12]], [[2z18]], [[2z19]], [[2vb1]], [[2hu3]], [[2hub]], [[2htx]], [[2hu1]], [[2yvb]], [[2epe]], [[2g4p]], [[2g4q]], [[2cgi]], [[2b5z]], [[2d4k]], [[2d91]], [[2f2n]], [[2fbb]], [[2c8o]], [[2c8p]], [[2a6u]], [[2aub]], [[2blx]], [[2bly]], [[2a7d]], [[2a7f]], [[1wtm]], [[1wtn]], [[1w6z]], [[1vdp]], [[1vdq]], [[1vds]], [[1vdt]], [[1ved]], [[1v7t]], [[1ps5]], [[2cds]], [[1lj3]], [[1lj4]], [[1lje]], [[1ljf]], [[1ljg]], [[1ljh]], [[1lji]], [[1ljj]], [[1ljk]], [[1jis]], [[1jit]], [[1jiy]], [[1jj0]], [[1jj1]], [[1jj3]], [[1iee]], [[1qio]], [[1f0w]], [[1f10]], [[1dpx]], [[1c10]], [[1qtk]], [[1lz8]], [[1lz9]], [[1bhz]], [[1bgi]], [[1bwh]], [[1bwi]], [[1bwj]], [[1bvx]], [[1hsw]], [[1hsx]], [[1lpi]], [[4lzt]], [[3lzt]], [[1aki]], [[1jpo]], [[1rfp]], [[193l]], [[194l]], [[5lym]], [[1lza]], [[3lyt]], [[4lyt]], [[5lyt]], [[6lyt]], [[2lzt]], [[1lzt]], [[1lzh]], [[2lzh]], [[7lyz]], [[1lyz]], [[2lyz]], [[3lyz]], [[4lyz]], [[5lyz]], [[6lyz]] - HEWL – chicken 
[[1xei]], [[1xej]], [[1xek]], [[1uco]], [[1lma]], [[4lym]] – HEWL low hydration 
[[1lsa]], [[1lsb]], [[1lsc]], [[1lsd]], [[1lse]], [[1lsf]], [[1lys]] – HEWL temperature influence 
[[2lym]], [[3lym]] – HEWL pressure influence 
[[132l]] – HEWL methylated 
[[1rcm]] – HEWL 3 S-S form 
[[2xbr]], [[2xbs]]- HEWL– Raman crystallography 
[[2zwb]], [[1io5]], [[1lzn]] - HEWL– Neutron 
[[1gxv]], [[1gxx]], [[1e8l]] - HEWL- NMR 
[[2hs7]], [[2hso]], [[2hs9]]- HEWL– Powder diffraction 
[[1ir7]], [[1ir8]], [[1ir9]], [[1ioq]], [[1ior]], [[1ios]], [[1iot]], [[1flq]], [[1flu]], [[1flw]], [[1fly]], [[1fn5]], [[1kxw]], [[1kxx]], [[1kxy]], [[1uia]], [[1uib]], [[1uic]], [[1uid]], [[1uie]], [[1uif]], [[1uig]], [[1uih]], [[1lsm]], [[1lsn]], [[1hel]], [[1hem]], [[1hen]], [[1heo]], [[1hep]], [[1heq]], [[1her]] – HEWL (mutant) 
[[1lyo]], [[2lyo]], [[3lyo]], [[4lyo]] – HEWL cross-linked 
[[1xft]] - tuLys – turkey - Powder diffraction 
[[1jse]], [[1tew]], [[135l]], [[2lz2]], [[1lz2]] – tuLys 
[[3lz2]] – tuLys - Laue 
[[3ab6]] – Lys + NAG3 – Hard clam 
[[2x8r]] – Lys GH25 – ''Aspergillus fumigatus'' 
[[3mgw]] – Lys G – Atlantic salmon 
[[3gxk]], [[3gxr]] – Lys G + NAG – Atlantic cod 
[[2fbd]] – HfLys 1 
[[3cb7]] – HfLys 2 
[[2zij]], [[2zik]], [[2zil]], [[2nwd]], [[1iwt]], [[1iwu]], [[1iwv]], [[1iww]], [[1iwx]], [[1iwy]], [[1iwz]], [[1jwr]], [[1jsf]], [[1rex]], [[1lz1]] – hLys – human 
[[1w08]], [[1ix0]], [[1ioc]], [[1ip1]], [[1ip2]], [[1ip3]], [[1ip4]], [[1ip5]], [[1ip6]], [[1ip7]], [[1qsw]], [[1gev]], [[1gez]], [[1gf0]], [[1gf3]], [[1gf4]], [[1gf5]], [[1gf6]], [[1gf7]], [[1i1z]], [[1i20]], [[1i22]], [[1gfr]], [[1gft]], [[1gfu]], [[1gfv]], [[1gf8]], [[1gf9]], [[1gfa]], [[1gfe]], [[1gfg]], [[1gfh]], [[1gfj]], [[1gfk]], [[1inu]], [[1gdx]], [[1ge0]], [[1ge1]], [[1ge2]], [[1ge3]], [[1ge4]], [[1gdw]], [[1gaz]], [[1gb0]], [[1gb2]], [[1gb3]], [[1gb5]], [[1gb6]], [[1gb7]], [[1gb8]], [[1gb9]], [[1gbo]], [[1gbw]], [[1gbx]], [[1gby]], [[1gbz]], [[1gay]], [[1eq4]], [[1eq5]], [[1eqe]], [[1c7p]], [[1di3]], [[1di4]], [[1di5]], [[1c43]], [[1c45]], [[1c46]], [[1ckg]], [[1cj6]], [[1cj7]], [[1cj8]], [[1cj9]], [[1ckc]], [[1ckd]], [[1ckf]], [[1ckh]], [[1b5z]], [[1b70]], [[1b7q]], [[1b7r]], [[1b7s]], [[1b7l]], [[1b7m]], [[1b7n]], [[1b7p]], [[1b5u]], [[1b5v]], [[1b5w]], [[1b5x]], [[1b5y]], [[1bb3]], [[1bb4]], [[2bqa]], [[2bqb]], [[2bqc]], [[2bqd]], [[2bqe]], [[2bqf]], [[2bqg]], [[2bqh]], [[2bqi]], [[2bqj]], [[2bqk]], [[2bql]], [[2bqm]], [[2bqn]], [[2bqo]], [[2mea]], [[2meb]], [[2mec]], [[2med]], [[2mee]], [[2mef]], [[2meg]], [[2meh]], [[2mei]], [[1wqm]], [[1wqn]], [[1wqo]], [[1wqp]], [[1wqq]], [[1wqr]], [[2heb]], [[2hea]], [[2hec]], [[2hed]], [[2hee]], [[2hef]], [[1jka]], [[1jkb]], [[1jkc]], [[1jkd]], [[1loz]], [[1lyy]], [[1oua]], [[1oub]], [[1ouc]], [[1oud]], [[1oue]], [[1ouf]], [[1oug]], [[1ouh]], [[1oui]], [[1ouj]], [[207l]], [[208l ]], [[1yam]], [[1yan]], [[1yao]], [[1yap]], [[1yaq]], [[1lmt]], [[1lhh]], [[1lhi]], [[1lhj]], [[1lhk]], [[1lhl]], [[133l]], [[134l]], [[1lz4]], [[1lz5]], [[1lz6]], [[1laa]], [[1tay]], [[1tby]], [[1tcy]], [[1tdy]], [[2lhm]], [[3lhm]] – hLys (mutant) 
[[1iy3]], [[1iy4]] – hLys - NMR 
[[2z2f]] – Lys – Bovine 
[[2cwi]], [[1el1]], [[1qqy]] – dLys - dog 
[[2z2e]] – dLys (mutant) 
[[1i56]] – dLys – NMR 
[[2dqa]] – Lys – ''Tapes japonica'' 
[[2gv0]] – Lys – Soft-shelled turtle 
[[1ivm]] – mLys M – NMR – mouse 
[[1jfx]] – Lys – ''Streptomyces coelicolor'' 
[[1gd6]] – Lys – ''Bombyx mori'' 
[[1jug]] – Lys – Echidna 
[[1dkj]] – BqLys – Bobwhite quail 
[[2ihl]] – Lys – Japanese quail 
[[1gbs]] – BsLys – Black swan 
[[1lmn]] – RtLys – Rainbow trout 
[[2eql]] – Lys – horse 
[[1ghl]] – phLys – pheasant 
[[1hhl]] – GfLys – Guinea fowl 
[[1lhm]] – Lys (mutant) – yeast 

===Lys small molecules complexes===

[[3fe0]], [[2d4i]], [[2d4j]], [[1v7s]] - HEWL+ D2O 
[[3m3u]] – HEWL Trp fluorescence 
[[2xjw]] - HEWL + CO 
[[1hf4]], [[1lks]] – HEWL + NO3 
[[3a34]], [[3ems]] - HEWL + arginine 
[[2xth]] – cLys + inhibitor K2PtBr6 
[[3a90]], [[3a91]], [[3a92]], [[3a93]], [[3a94]], [[3a95]], [[3a96]], [[3kam]], [[2pc2]], [[2bpu]], [[1t3p]], [[1h87]] – HEWL + rare earth 
[[2d6b]], [[2hg0]], [[1vat]], [[1gwd]], [[1b2k]], [[1lkr]], [[1azf]], [[8lyz]]- HEWL+ halogen 
[[1vat]] - HEWL + Xe 
[[1n4f]] - HEWL + As 
[[2i6z]] - HEWL + Pt drug 
[[2zyp]] - HEWL + poly (allyl amine) 
[[2f30]], [[2f4a]] – HEWL + urea derivative 
[[2f4g]], [[1ykx]], [[1yky]], [[1ykz]], [[1yl0]], [[1yl1]], [[1z55]] - HEWL + alcohol 
[[1dpw]] – HEWL + MPD 
[[1lcn]] – HEWL + SCN 
[[2zxs]] - HEWL with glycine-amide 
[[2h9j]], [[2h9k]], [[1yik]], [[1yil]] - HEWL + cyclam derivative 
[[1b0d]] – HEWL + p-toluene-sulfonate 
[[2q0m]] - HEWL + tricarbonylmanganese 
[[2war]] – HEWL (mutant) + chitopentaose 
[[2h5z]] – HfLys 1 + chitotetraose – House fly 
[[1hnl]] – hLys + glutathione 
[[1dkk]] – BqLys + NO3 

===Lys complex with glucoside===

[[3a3q]] – HEWL (mutant) + NAG 
[[1sf4]], [[1sf6]], [[1sf7]], [[1sfb]], [[1sfg]], [[1ja2]], [[1ja4]], [[1ja6]], [[1ja7]] – HEWL + NAG oligosaccharide – Powder diffraction 
[[1ubz]], [[1d6p]], [[1d6q]], [[1bb5]] – hLys (mutant) + glycoside 
[[1uc0]], [[1re2]], [[1rem]], [[1rey]], [[1rez]], [[1lzr]], [[1lzs]] - hLys + glycoside 
[[1ljn]], [[1jef]], [[1lzy]] – tuLys + glycoside 
[[1h6m]], [[1at5]], [[1at6]], [[1lzb]], [[1lzc]], [[1lzd]], [[1lze]], [[1lzg]], [[1hew ]]– HEWL + glycoside 
[[1lsy]], [[1lsz]] - HEWL (mutant) + glycoside 
[[1bb6]], [[1bb7]] – RtLys + glycoside 
[[1lmc]] – RtLys + bulgecin 
[[1lmo]], [[1lmp]], [[1lmq]] – RtLys + glucoside 
[[1lsp]] – BsLys + bulgecin 
[[153l]], [[154l]] – Lys +glucoside – goose 

===Phage Lys===

[[2oe4]], [[2oe7]], [[2oe9]], [[2oea]], [[1swz]], [[1cx6]], [[1qtc]], [[1qtd]], [[1qth]], [[1qsb]], [[1qs5]], [[1qs9]], [[1qtb]], [[256l]], [[206l]], [[167l]], [[168l]], [[169l]], [[170l]], [[171l]], [[172l]], [[173l]], [[174l]], [[175l]], [[176l]], [[177l]], [[178l]], [[181l]], [[182l]], [[183l]], [[184l]], [[185l]], [[186l]], [[187l]], [[188l]], [[1nhb]], [[137l]], [[216l]], [[152l]], [[149l]], [[150l]], [[151l]], [[1lyd]], [[2lzm]] - T4Lys – Enterobacteria phage T4 
[[138l]] – T4Lys cross-linked 
[[4lzm]], [[5lzm]], [[6lzm]], [[7lzm]] – T4Lys ionic strength 
[[3l2x]], [[3k2r]], [[3g3v]], [[3g3w]], [[3g3x]], [[2q9d]], [[2q9e]], [[2igc]], [[2ntg]], [[2nth]], [[2ou8]], [[2ou9]], [[1zur]], [[1zwn]], [[1zyt]], [[2cuu]], [[2a4t]] – T4Lys (mutant) spin labeled 
[[3l64]], [[3hwl]], [[3jr6]], [[3gui]], [[3c7w]], [[3c7y]], [[3c7z]], [[3c80]], [[3c81]], [[3c82]], [[3c83]], [[3c8q]], [[3c8r]], [[3c8s]], [[3cdo]], [[3cdq]], [[3cdr]], [[3cdt]], [[3cdv]], [[3f8v]], [[3f9l]], [[3fa0]], [[3fad]], [[3fi5]], [[3dke]], [[3dmv]], [[2o4w]], [[2o79]], [[2o7a]], [[2huk]], [[2hul]], [[2hum]], [[2b7x]], [[2b6t]], [[2b6w]], [[2b6x]], [[2b6y]], [[2b6z]], [[2b70]], [[2b72]], [[2b73]], [[2b74]], [[2b75]], [[1sx7]], [[1swy]], [[1sx2]], [[1t6h]], [[1ssw]], [[1ssy]], [[1t8f]], [[1t8g]], [[1t8a]], [[1t97]], [[1p56]], [[1p5c]], [[1p2l]], [[1p2r]], [[1p36]], [[1p37]], [[1p3n]], [[1p46]], [[1p64]], [[1p6y]], [[1p7s]], [[1pqd]], [[1pqi]], [[1pqj]], [[1pqk]], [[1pqm]], [[1pqo]], [[1oyu]], [[1ks3]], [[1kw5]], [[1kw7]], [[1ky0]], [[1ky1]], [[1l0j]], [[1l0k]], [[1lw9]], [[1lwg]], [[1lwk]], [[1lpy]], [[1llh]], [[1lgu]], [[1li6]], [[1jtm]], [[1jtn]], [[1jqu]], [[1kni]], [[1g06]], [[1g07]], [[1g0g]], [[1g0j]], [[1g0k]], [[1g0l]], [[1g0m]], [[1g0p]], [[1g0q]], [[1g1v]], [[1g1w]], [[1i6s]], [[257l]], [[258l]], [[260l]], [[1epy]], [[1b6i]], [[1cu6]], [[1d9w]], [[1ctw]], [[1cu0]], [[1cu2]], [[1cu3]], [[1cu5]], [[1cv1]], [[1cv4]], [[1cv5]], [[1cv6]], [[1cvk]], [[1cx7]], [[1d2w]], [[1d2y]], [[1d3f]], [[1d3j]], [[1d3m]], [[1d3n]], [[1cv3]], [[1qt3]], [[1qt4]], [[1qt5]], [[1qt6]], [[1qt7]], [[1qt8]], [[1qtv]], [[1qtz]], [[1qud]], [[1qug]], [[1quh]], [[1quo]], [[1qsq]], [[261l]], [[262l]], [[259l]], [[220l]], [[222l]], [[223l]], [[225l]], [[226l]], [[227l]], [[228l]], [[229l]], [[235l]], [[236l]], [[237l]], [[238l]], [[239l]], [[240l]], [[241l]], [[242l]], [[243l]], [[244l]], [[245l]], [[246l]], [[247l]], [[248l]], [[249l]], [[250l]], [[251l]], [[252l]], [[253l]], [[254l]], [[255l]], [[230l]], [[231l]], [[232l]], [[233l]], [[234l]], [[209l]], [[210l]], [[211l]], [[212l]], [[213l]], [[214l]], [[215l]], [[218l]], [[219l]], [[180l]], [[195l]], [[196l]], [[197l]], [[198l]], [[199l]], [[200l]], [[190l]], [[191l]], [[192l]], [[189l]], [[155l]], [[156l]], [[157l]], [[158l]], [[159l]], [[160l]], [[161l]], [[162l]], [[163l]], [[164l]], [[165l]], [[166l]], [[129l]], [[130l]], [[131l]], [[140l]], [[141l]], [[142l]], [[143l]], [[144l]], [[145l]], [[146l]], [[147l]], [[201l]], [[205l]], [[221l]], [[224l]], [[102l]], [[103l]], [[104l]], [[107l]], [[108l]], [[109l]], [[110l]], [[111l]], [[112l]], [[113l]], [[114l]], [[115l]], [[118l]], [[119l]], [[120l]], [[122l]], [[123l]], [[125l]], [[126l]], [[127l]], [[128l]], [[1dya]], [[1dyb]], [[1dyc]], [[1dyd]], [[1dye]], [[1dyf]], [[1dyg]], [[1l00]], [[1l85]], [[1l86]], [[1l87]], [[1l88]], [[1l89]], [[1l90]], [[1l91]], [[1l92]], [[1l93]], [[1l94]], [[1l95]], [[1l96]], [[1l97]], [[1l98]], [[1l99]], [[1lye]], [[1lyf]], [[1lyg]], [[1lyh]], [[1lyi]], [[1lyj]], [[217l]], [[1tla]], [[1l77]], [[1l79]], [[1l80]], [[1l81]], [[1l82]], [[2l78]], [[1l36]], [[1l37]], [[1l38]], [[1l39]], [[1l40]], [[1l41]], [[1l42]], [[1l43]], [[1l44]], [[1l45]], [[1l46]], [[1l47]], [[1l48]], [[1l49]], [[1l50]], [[1l51]], [[1l52]], [[1l53]], [[1l54]], [[1l55]], [[1l56]], [[1l57]], [[1l58]], [[1l59]], [[1l60]], [[1l61]], [[1l62]], [[1l63]], [[1l64]], [[1l65]], [[1l66]], [[1l67]], [[1l68]], [[1l69]], [[1l70]], [[1l71]], [[1l72]], [[1l73]], [[1l74]], [[1l75]], [[1l76]], [[1l17]], [[1l18]], [[1l19]], [[1l20]], [[1l21]], [[1l22]], [[1l23]], [[1l24]], [[1l25]], [[1l26]], [[1l27]], [[1l28]], [[1l29]], [[1l30]], [[1l31]], [[1l32]], [[1l33]], [[1l34]], [[1l35]], [[3lzm]], [[1l01]], [[1l02]], [[1l03]], [[1l04]], [[1l05]], [[1l06]], [[1l07]], [[1l08]], [[1l09]], [[1l10]], [[1l11]], [[1l12]], [[1l13]], [[1l14]], [[1l15]], [[1l16]] – T4Lys (mutant) 
[[1c60]], [[1c61]], [[1c62]], [[1c63]], [[1c64]], [[1c65]], [[1c66]], [[1c67]], [[1c68]], [[1c69]], [[1c6a]], [[1c6b]], [[1c6c]], [[1c6d]], [[1c6e]], [[1c6f]], [[1c6g]], [[1c6h]], [[1c6i]], [[1c6j]], [[1c6k]], [[1c6l]], [[1c6m]], [[1c6n]], [[1c6p]], [[1c6q]], [[1c6t]] - T4Lys (mutant) + noble gas 
[[3ht6]], [[3ht7]], [[3ht8]], [[3ht9]], [[3htb]], [[3hu8]], [[3huq]], [[3guj]], [[3guk]], [[3gul]], [[3gum]], [[3gun]], [[3guo]], [[3gup]], [[3dmx]], [[3dmz]], [[3dn0]], [[3dn1]], [[3dn2]], [[3dn3]], [[3dn4]], [[3dn6]], [[3dn8]], [[3dna]], [[2rb1]], [[2ray]], [[2raz]], [[2rb0]], [[2rb2]], [[2rbn]], [[2rbo]], [[2rbq]], [[2rbr]], [[2rbs]], [[2oty]],[[2otz]], [[1owy]], [[1owz]], [[1ov5]], [[1ov7]], [[1ovh]], [[1ovj]], [[1ovk]], [[1lgw]], [[1lgx]], [[1li2]], [[1li3]], [[1l83]], [[1l84]] – T4Lys (mutant) + benzene derivative 
[[3htd]], [[3htf]], [[3htg]], [[3hu9]], [[3hua]], [[3huk]], [[3hh3]], [[3hh4]], [[3hh5]], [[3hh6]], [[2rbp]], [[2ou0]], [[2f2q]], [[2f32]], [[2f47]], [[1xep]] – T4Lys (mutant) + inhibitor 
[[148l]] - T4Lys (mutant) + glucoside 
[[3d3d]], [[1d9u]] – lamLys + chitohexasaccharide 
[[1am7]] – lamLys - Enterobacteria phage λ 
[[2anv]], [[2anx]] – Lys (mutant)]] - Enterobacteria phage p22 
[[1xjt]], [[1xju]] - Lys - Enterobacteria phage p1 
[[1lba]] - T7Lys - Enterobacteria phage T7 

===Lys protein complex===

[[3m18]], [[3g3a]], [[3g3b]] - HEWL + Variable lymphocyte receptor – Marine lamprey 
[[3a67]], [[3a6b]], [[3a6c]], [[2yss]], [[2eiz]], [[2dqc]], [[2dqd]], [[2dqe]], [[2dqf]], [[2dqg]], [[2dqh]], [[2dqi]], [[2dqj]], [[1j1o]], [[1j1p]], [[1j1x]], [[1ic4]], [[1ic5]], [[1ic7]] – HEWL + mLys antibody HYHEL-10 (mutant) 
[[1xgp]], [[1xgq]], [[1xgr]], [[1xgt]], [[1xgu]] – HEWL + mLys antibody HYHEL-63 
[[3d9a]], [[2eks]], [[1ua6]], [[1c08]], [[3hfm]] – HEWL + mLys antibody HYHEL-10 
[[1uac]] - tuLys C + mLys antibody HYHEL-10 
[[1yqv]], [[2iff]] – HEWL + mLys antibody HYHEL-5 
[[1bql]] – BqLys + mLys antibody HYHEL-5 
[[1ndg]] – HEWL + mLys antibody HYHEL-8 
[[1ndm]] – HEWL + mLys antibody HYHEL-26 
[[1dqj]] - HEWL + mLys antibody HYHEL-63 
[[1nby]], [[1nbz]] – HEWL (mutant) + mLys antibody HYHEL-63 
[[1g7h]], [[1g7i]], [[1g7j]], [[1g7l]], [[1g7m]], [[1kip]], [[1kiq]], [[1kir]] – HEWL + mAnti-HEWL monoclonal antibody (mutant) 
[[1mlc]], [[1vfb]] - HEWL + mIGG1-κ D44.1 FAB 
[[1a2y]] - HEWL (mutant) + mIGG1-κ D1.3 FV 
[[1fdl]] - HEWL + mIGG1-κ D1.3 FAB 
[[1jhl]] – phLys + mIGG1-κ D11.15 FV 
[[1fbi]] – GfLys + mIGG1 F9.13.7 FAB 
[[2znw]], [[2znx]] – HEWL + hSCFV10 antibody 
[[1bvk]] - HEWL + hAnti Lys FV antibody 
[[1dzb]] – tuLys + mSCFV 1F9 
[[1zv5]], [[1zvh]], [[1zvy]], [[1zmy]], [[1ri8]], [[1rjc]], [[1xfp]], [[1jtp]], [[1jtt]], [[1jto]], [[1mel]] - HEWL + cAntibody heavy chain domain – camel 
[[1op9]] - hLys C + cAntibody heavy chain domain 
[[3otp]] – HEWL + EcProtease DO – ''Escherichia coli'' 
[[3f6z]] - HEWL + MLIC – ''Pseudomonas aeruginosa'' 
[[3eba]] – hLys C + hCABHUL6 
[[2qb0]], [[2qar]] – T4Lys/E80 TELSAM domain 
[[2i25]], [[2i26]] - HEWL +NsAntigen receptor PBLA8 variable domain – Nurse shark 
[[1sq2]], [[1t6v]] – HEWL +NsNew Antigen receptor variable domain 
[[1gpq]] – HEWL + EcInhibitor of Vertebrate Lys 
[[1aro]] – T7Lys + T7 RNA polymerase 

===Some Useful External Links===
[http://en.wikipedia.org/wiki/Lysozyme Lysozyme]

[http://en.wikipedia.org/wiki/Glycoside_hydrolase#Retaining_glycoside_hydrolases Retaining Glycoside Hydrolases]

===References===
<references/>

Hen Egg-White (HEW) Lysozyme

2011-03-31T01:16:36Z

Anne Goodling:

<applet load='aln_1H6M_to_1HEW_2.pdb' size='300' frame='true' align='right' caption=' Hen Egg White (HEW) Lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to the active site, PDBid 1HEW' scene='User:Judy_Voet/Lysozyme/Lysozyme1/16' />
Lysozyme was the first enzyme whose X-ray structure was determined <ref> PMID 5840126</ref><ref>Phillips, D. C. The hen egg white lysozyme molecule. Proc. Natl Acad. Sci. USA 57, 483-495 (1967)</ref>. This <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>scene </scene> shows Hen Egg White (HEW) lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to a cleft in the enzyme. David Phillips, who determined the structure in 1965, saw that the cleft was large enough to fit three more saccharide units. He therefore built a model extending the trisaccharide to a
<scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> that fits into the cleft, labeling the sugar subsites A-F<ref> coordinates of the model kindly provided by Louise Johnson</ref>. Alternately click on <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>trisaccharide</scene> and <scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> to turn the modeled portion of the hexasaccharide on and off.
The interesting thing about the model was that the only way that the hexasaccharide would fit into the cleft was if the 4th saccharide (in subsite D) was strained into a <scene name='User:Judy_Voet/Lysozyme/Half-chair/2'>half-chair conformation</scene>. This conformation is what would be necessary for the formation of an oxocarbenium ion (oxionium ion). When the model was studied, <scene name='User:Judy_Voet/Lysozyme/Glu_35/1'>Glu 35</scene> was found to be in an ideal location to act as a general acid catalyst, 3.34 Angstroms from the bridging oxygen between the 4th and 5th saccharide units. <scene name='User:Judy_Voet/Lysozyme/Asp_52/2'>Asp 52</scene> appeared to be too far away (2.69 angstroms) in the static lysozyme structure to have formed a covalent bond with C1 of the half-chair model in the D site, and no covalent intermediate had ever been detected, so Phillips proposed that it acted as an electrostatic stabilizer of the oxonium ion (referred to as The Phillips Mechanism).
<applet load='aln_1H6M_to_1HEW_2.pdb' size='300' frame='true' align='left' caption='NAG-2-deoxy-2-fluoro-glucosyl fluoride (NAG2FGlcF) bound to Glu35Gln HEW Lysozyme PDBid 1H6M' scene='User:Judy_Voet/Lysozyme/1h6m/3'/>

Then, in 2001, Stephen Withers published <scene name='User:Judy_Voet/Lysozyme/1h6m/3'>1H6M</scene>,<ref>PMID 11518970</ref> in which Glu 35 had been mutated to Gln to remove the general acid catalyst. The substrate contained NAG-2-fluoro-glucosyl fluoride (NAG2FGlcF). The fluoro group on C-1 does not require acid catalysis to be a good leaving group, and the remaining saccharide, in the absence of the acid necessary to catalyse the second step of the reaction, was demonstrated to form a <scene name='User:Judy_Voet/Lysozyme/Covalent/1'> covalent intermediate</scene>. In this <scene name='User:Judy_Voet/Lysozyme/Superposition/2'>superposition</scene> of the half chair model with 1HEW (greens) and the covalent intermediate in 1H6M (blues), note the relatively small motions of Asp 52 and C1 of the sugar ring in going from the model to the covalent intermediate. to observe the motion from the <scene name='User:Judy_Voet/Lysozyme/Asp52_halfchair/1'>half-chair</scene> to the <scene name='User:Judy_Voet/Lysozyme/Covalent/2'>covalent intermediate</scene> just toggle between the two green links.

== 3D Structures of Lysozyme ==

===Lys===

[[2x0a]], [[3iju]], [[3ijv]], [[3a8z]], [[2w1y]], [[2w1m]], [[2w1x]], [[2w1l]], [[3e3d]], [[3exd]], [[2zq3]], [[2zq4]], [[3b72]], [[3b6l]], [[2z12]], [[2z18]], [[2z19]], [[2vb1]], [[2hu3]], [[2hub]], [[2htx]], [[2hu1]], [[2yvb]], [[2epe]], [[2g4p]], [[2g4q]], [[2cgi]], [[2b5z]], [[2d4k]], [[2d91]], [[2f2n]], [[2fbb]], [[2c8o]], [[2c8p]], [[2a6u]], [[2aub]], [[2blx]], [[2bly]], [[2a7d]], [[2a7f]], [[1wtm]], [[1wtn]], [[1w6z]], [[1vdp]], [[1vdq]], [[1vds]], [[1vdt]], [[1ved]], [[1v7t]], [[1ps5]], [[2cds]], [[1lj3]], [[1lj4]], [[1lje]], [[1ljf]], [[1ljg]], [[1ljh]], [[1lji]], [[1ljj]], [[1ljk]], [[1jis]], [[1jit]], [[1jiy]], [[1jj0]], [[1jj1]], [[1jj3]], [[1iee]], [[1qio]], [[1f0w]], [[1f10]], [[1dpx]], [[1c10]], [[1qtk]], [[1lz8]], [[1lz9]], [[1bhz]], [[1bgi]], [[1bwh]], [[1bwi]], [[1bwj]], [[1bvx]], [[1hsw]], [[1hsx]], [[1lpi]], [[4lzt]], [[3lzt]], [[1aki]], [[1jpo]], [[1rfp]], [[193l]], [[194l]], [[5lym]], [[1lza]], [[3lyt]], [[4lyt]], [[5lyt]], [[6lyt]], [[2lzt]], [[1lzt]], [[1lzh]], [[2lzh]], [[7lyz]], [[1lyz]], [[2lyz]], [[3lyz]], [[4lyz]], [[5lyz]], [[6lyz]] - HEWL – chicken 
[[1xei]], [[1xej]], [[1xek]], [[1uco]], [[1lma]], [[4lym]] – HEWL low hydration 
[[1lsa]], [[1lsb]], [[1lsc]], [[1lsd]], [[1lse]], [[1lsf]], [[1lys]] – HEWL temperature influence 
[[2lym]], [[3lym]] – HEWL pressure influence 
[[132l]] – HEWL methylated 
[[1rcm]] – HEWL 3 S-S form 
[[2xbr]], [[2xbs]]- HEWL– Raman crystallography 
[[2zwb]], [[1io5]], [[1lzn]] - HEWL– Neutron 
[[1gxv]], [[1gxx]], [[1e8l]] - HEWL- NMR 
[[2hs7]], [[2hso]], [[2hs9]]- HEWL– Powder diffraction 
[[1ir7]], [[1ir8]], [[1ir9]], [[1ioq]], [[1ior]], [[1ios]], [[1iot]], [[1flq]], [[1flu]], [[1flw]], [[1fly]], [[1fn5]], [[1kxw]], [[1kxx]], [[1kxy]], [[1uia]], [[1uib]], [[1uic]], [[1uid]], [[1uie]], [[1uif]], [[1uig]], [[1uih]], [[1lsm]], [[1lsn]], [[1hel]], [[1hem]], [[1hen]], [[1heo]], [[1hep]], [[1heq]], [[1her]] – HEWL (mutant) 
[[1lyo]], [[2lyo]], [[3lyo]], [[4lyo]] – HEWL cross-linked 
[[1xft]] - tuLys – turkey - Powder diffraction 
[[1jse]], [[1tew]], [[135l]], [[2lz2]], [[1lz2]] – tuLys 
[[3lz2]] – tuLys - Laue 
[[3ab6]] – Lys + NAG3 – Hard clam 
[[2x8r]] – Lys GH25 – ''Aspergillus fumigatus'' 
[[3mgw]] – Lys G – Atlantic salmon 
[[3gxk]], [[3gxr]] – Lys G + NAG – Atlantic cod 
[[2fbd]] – HfLys 1 
[[3cb7]] – HfLys 2 
[[2zij]], [[2zik]], [[2zil]], [[2nwd]], [[1iwt]], [[1iwu]], [[1iwv]], [[1iww]], [[1iwx]], [[1iwy]], [[1iwz]], [[1jwr]], [[1jsf]], [[1rex]], [[1lz1]] – hLys – human 
[[1w08]], [[1ix0]], [[1ioc]], [[1ip1]], [[1ip2]], [[1ip3]], [[1ip4]], [[1ip5]], [[1ip6]], [[1ip7]], [[1qsw]], [[1gev]], [[1gez]], [[1gf0]], [[1gf3]], [[1gf4]], [[1gf5]], [[1gf6]], [[1gf7]], [[1i1z]], [[1i20]], [[1i22]], [[1gfr]], [[1gft]], [[1gfu]], [[1gfv]], [[1gf8]], [[1gf9]], [[1gfa]], [[1gfe]], [[1gfg]], [[1gfh]], [[1gfj]], [[1gfk]], [[1inu]], [[1gdx]], [[1ge0]], [[1ge1]], [[1ge2]], [[1ge3]], [[1ge4]], [[1gdw]], [[1gaz]], [[1gb0]], [[1gb2]], [[1gb3]], [[1gb5]], [[1gb6]], [[1gb7]], [[1gb8]], [[1gb9]], [[1gbo]], [[1gbw]], [[1gbx]], [[1gby]], [[1gbz]], [[1gay]], [[1eq4]], [[1eq5]], [[1eqe]], [[1c7p]], [[1di3]], [[1di4]], [[1di5]], [[1c43]], [[1c45]], [[1c46]], [[1ckg]], [[1cj6]], [[1cj7]], [[1cj8]], [[1cj9]], [[1ckc]], [[1ckd]], [[1ckf]], [[1ckh]], [[1b5z]], [[1b70]], [[1b7q]], [[1b7r]], [[1b7s]], [[1b7l]], [[1b7m]], [[1b7n]], [[1b7p]], [[1b5u]], [[1b5v]], [[1b5w]], [[1b5x]], [[1b5y]], [[1bb3]], [[1bb4]], [[2bqa]], [[2bqb]], [[2bqc]], [[2bqd]], [[2bqe]], [[2bqf]], [[2bqg]], [[2bqh]], [[2bqi]], [[2bqj]], [[2bqk]], [[2bql]], [[2bqm]], [[2bqn]], [[2bqo]], [[2mea]], [[2meb]], [[2mec]], [[2med]], [[2mee]], [[2mef]], [[2meg]], [[2meh]], [[2mei]], [[1wqm]], [[1wqn]], [[1wqo]], [[1wqp]], [[1wqq]], [[1wqr]], [[2heb]], [[2hea]], [[2hec]], [[2hed]], [[2hee]], [[2hef]], [[1jka]], [[1jkb]], [[1jkc]], [[1jkd]], [[1loz]], [[1lyy]], [[1oua]], [[1oub]], [[1ouc]], [[1oud]], [[1oue]], [[1ouf]], [[1oug]], [[1ouh]], [[1oui]], [[1ouj]], [[207l]], [[208l ]], [[1yam]], [[1yan]], [[1yao]], [[1yap]], [[1yaq]], [[1lmt]], [[1lhh]], [[1lhi]], [[1lhj]], [[1lhk]], [[1lhl]], [[133l]], [[134l]], [[1lz4]], [[1lz5]], [[1lz6]], [[1laa]], [[1tay]], [[1tby]], [[1tcy]], [[1tdy]], [[2lhm]], [[3lhm]] – hLys (mutant) 
[[1iy3]], [[1iy4]] – hLys - NMR 
[[2z2f]] – Lys – Bovine 
[[2cwi]], [[1el1]], [[1qqy]] – dLys - dog 
[[2z2e]] – dLys (mutant) 
[[1i56]] – dLys – NMR 
[[2dqa]] – Lys – ''Tapes japonica'' 
[[2gv0]] – Lys – Soft-shelled turtle 
[[1ivm]] – mLys M – NMR – mouse 
[[1jfx]] – Lys – ''Streptomyces coelicolor'' 
[[1gd6]] – Lys – ''Bombyx mori'' 
[[1jug]] – Lys – Echidna 
[[1dkj]] – BqLys – Bobwhite quail 
[[2ihl]] – Lys – Japanese quail 
[[1gbs]] – BsLys – Black swan 
[[1lmn]] – RtLys – Rainbow trout 
[[2eql]] – Lys – horse 
[[1ghl]] – phLys – pheasant 
[[1hhl]] – GfLys – Guinea fowl 
[[1lhm]] – Lys (mutant) – yeast 

===Lys small molecules complexes===

[[3fe0]], [[2d4i]], [[2d4j]], [[1v7s]] - HEWL+ D2O 
[[3m3u]] – HEWL Trp fluorescence 
[[2xjw]] - HEWL + CO 
[[1hf4]], [[1lks]] – HEWL + NO3 
[[3a34]], [[3ems]] - HEWL + arginine 
[[2xth]] – cLys + inhibitor K2PtBr6 
[[3a90]], [[3a91]], [[3a92]], [[3a93]], [[3a94]], [[3a95]], [[3a96]], [[3kam]], [[2pc2]], [[2bpu]], [[1t3p]], [[1h87]] – HEWL + rare earth 
[[2d6b]], [[2hg0]], [[1vat]], [[1gwd]], [[1b2k]], [[1lkr]], [[1azf]], [[8lyz]]- HEWL+ halogen 
[[1vat]] - HEWL + Xe 
[[1n4f]] - HEWL + As 
[[2i6z]] - HEWL + Pt drug 
[[2zyp]] - HEWL + poly (allyl amine) 
[[2f30]], [[2f4a]] – HEWL + urea derivative 
[[2f4g]], [[1ykx]], [[1yky]], [[1ykz]], [[1yl0]], [[1yl1]], [[1z55]] - HEWL + alcohol 
[[1dpw]] – HEWL + MPD 
[[1lcn]] – HEWL + SCN 
[[2zxs]] - HEWL with glycine-amide 
[[2h9j]], [[2h9k]], [[1yik]], [[1yil]] - HEWL + cyclam derivative 
[[1b0d]] – HEWL + p-toluene-sulfonate 
[[2q0m]] - HEWL + tricarbonylmanganese 
[[2war]] – HEWL (mutant) + chitopentaose 
[[2h5z]] – HfLys 1 + chitotetraose – House fly 
[[1hnl]] – hLys + glutathione 
[[1dkk]] – BqLys + NO3 

===Lys complex with glucoside===

[[3a3q]] – HEWL (mutant) + NAG 
[[1sf4]], [[1sf6]], [[1sf7]], [[1sfb]], [[1sfg]], [[1ja2]], [[1ja4]], [[1ja6]], [[1ja7]] – HEWL + NAG oligosaccharide – Powder diffraction 
[[1ubz]], [[1d6p]], [[1d6q]], [[1bb5]] – hLys (mutant) + glycoside 
[[1uc0]], [[1re2]], [[1rem]], [[1rey]], [[1rez]], [[1lzr]], [[1lzs]] - hLys + glycoside 
[[1ljn]], [[1jef]], [[1lzy]] – tuLys + glycoside 
[[1h6m]], [[1at5]], [[1at6]], [[1lzb]], [[1lzc]], [[1lzd]], [[1lze]], [[1lzg]], [[1hew ]]– HEWL + glycoside 
[[1lsy]], [[1lsz]] - HEWL (mutant) + glycoside 
[[1bb6]], [[1bb7]] – RtLys + glycoside 
[[1lmc]] – RtLys + bulgecin 
[[1lmo]], [[1lmp]], [[1lmq]] – RtLys + glucoside 
[[1lsp]] – BsLys + bulgecin 
[[153l]], [[154l]] – Lys +glucoside – goose 

===Phage Lys===

[[2oe4]], [[2oe7]], [[2oe9]], [[2oea]], [[1swz]], [[1cx6]], [[1qtc]], [[1qtd]], [[1qth]], [[1qsb]], [[1qs5]], [[1qs9]], [[1qtb]], [[256l]], [[206l]], [[167l]], [[168l]], [[169l]], [[170l]], [[171l]], [[172l]], [[173l]], [[174l]], [[175l]], [[176l]], [[177l]], [[178l]], [[181l]], [[182l]], [[183l]], [[184l]], [[185l]], [[186l]], [[187l]], [[188l]], [[1nhb]], [[137l]], [[216l]], [[152l]], [[149l]], [[150l]], [[151l]], [[1lyd]], [[2lzm]] - T4Lys – Enterobacteria phage T4 
[[138l]] – T4Lys cross-linked 
[[4lzm]], [[5lzm]], [[6lzm]], [[7lzm]] – T4Lys ionic strength 
[[3l2x]], [[3k2r]], [[3g3v]], [[3g3w]], [[3g3x]], [[2q9d]], [[2q9e]], [[2igc]], [[2ntg]], [[2nth]], [[2ou8]], [[2ou9]], [[1zur]], [[1zwn]], [[1zyt]], [[2cuu]], [[2a4t]] – T4Lys (mutant) spin labeled 
[[3l64]], [[3hwl]], [[3jr6]], [[3gui]], [[3c7w]], [[3c7y]], [[3c7z]], [[3c80]], [[3c81]], [[3c82]], [[3c83]], [[3c8q]], [[3c8r]], [[3c8s]], [[3cdo]], [[3cdq]], [[3cdr]], [[3cdt]], [[3cdv]], [[3f8v]], [[3f9l]], [[3fa0]], [[3fad]], [[3fi5]], [[3dke]], [[3dmv]], [[2o4w]], [[2o79]], [[2o7a]], [[2huk]], [[2hul]], [[2hum]], [[2b7x]], [[2b6t]], [[2b6w]], [[2b6x]], [[2b6y]], [[2b6z]], [[2b70]], [[2b72]], [[2b73]], [[2b74]], [[2b75]], [[1sx7]], [[1swy]], [[1sx2]], [[1t6h]], [[1ssw]], [[1ssy]], [[1t8f]], [[1t8g]], [[1t8a]], [[1t97]], [[1p56]], [[1p5c]], [[1p2l]], [[1p2r]], [[1p36]], [[1p37]], [[1p3n]], [[1p46]], [[1p64]], [[1p6y]], [[1p7s]], [[1pqd]], [[1pqi]], [[1pqj]], [[1pqk]], [[1pqm]], [[1pqo]], [[1oyu]], [[1ks3]], [[1kw5]], [[1kw7]], [[1ky0]], [[1ky1]], [[1l0j]], [[1l0k]], [[1lw9]], [[1lwg]], [[1lwk]], [[1lpy]], [[1llh]], [[1lgu]], [[1li6]], [[1jtm]], [[1jtn]], [[1jqu]], [[1kni]], [[1g06]], [[1g07]], [[1g0g]], [[1g0j]], [[1g0k]], [[1g0l]], [[1g0m]], [[1g0p]], [[1g0q]], [[1g1v]], [[1g1w]], [[1i6s]], [[257l]], [[258l]], [[260l]], [[1epy]], [[1b6i]], [[1cu6]], [[1d9w]], [[1ctw]], [[1cu0]], [[1cu2]], [[1cu3]], [[1cu5]], [[1cv1]], [[1cv4]], [[1cv5]], [[1cv6]], [[1cvk]], [[1cx7]], [[1d2w]], [[1d2y]], [[1d3f]], [[1d3j]], [[1d3m]], [[1d3n]], [[1cv3]], [[1qt3]], [[1qt4]], [[1qt5]], [[1qt6]], [[1qt7]], [[1qt8]], [[1qtv]], [[1qtz]], [[1qud]], [[1qug]], [[1quh]], [[1quo]], [[1qsq]], [[261l]], [[262l]], [[259l]], [[220l]], [[222l]], [[223l]], [[225l]], [[226l]], [[227l]], [[228l]], [[229l]], [[235l]], [[236l]], [[237l]], [[238l]], [[239l]], [[240l]], [[241l]], [[242l]], [[243l]], [[244l]], [[245l]], [[246l]], [[247l]], [[248l]], [[249l]], [[250l]], [[251l]], [[252l]], [[253l]], [[254l]], [[255l]], [[230l]], [[231l]], [[232l]], [[233l]], [[234l]], [[209l]], [[210l]], [[211l]], [[212l]], [[213l]], [[214l]], [[215l]], [[218l]], [[219l]], [[180l]], [[195l]], [[196l]], [[197l]], [[198l]], [[199l]], [[200l]], [[190l]], [[191l]], [[192l]], [[189l]], [[155l]], [[156l]], [[157l]], [[158l]], [[159l]], [[160l]], [[161l]], [[162l]], [[163l]], [[164l]], [[165l]], [[166l]], [[129l]], [[130l]], [[131l]], [[140l]], [[141l]], [[142l]], [[143l]], [[144l]], [[145l]], [[146l]], [[147l]], [[201l]], [[205l]], [[221l]], [[224l]], [[102l]], [[103l]], [[104l]], [[107l]], [[108l]], [[109l]], [[110l]], [[111l]], [[112l]], [[113l]], [[114l]], [[115l]], [[118l]], [[119l]], [[120l]], [[122l]], [[123l]], [[125l]], [[126l]], [[127l]], [[128l]], [[1dya]], [[1dyb]], [[1dyc]], [[1dyd]], [[1dye]], [[1dyf]], [[1dyg]], [[1l00]], [[1l85]], [[1l86]], [[1l87]], [[1l88]], [[1l89]], [[1l90]], [[1l91]], [[1l92]], [[1l93]], [[1l94]], [[1l95]], [[1l96]], [[1l97]], [[1l98]], [[1l99]], [[1lye]], [[1lyf]], [[1lyg]], [[1lyh]], [[1lyi]], [[1lyj]], [[217l]], [[1tla]], [[1l77]], [[1l79]], [[1l80]], [[1l81]], [[1l82]], [[2l78]], [[1l36]], [[1l37]], [[1l38]], [[1l39]], [[1l40]], [[1l41]], [[1l42]], [[1l43]], [[1l44]], [[1l45]], [[1l46]], [[1l47]], [[1l48]], [[1l49]], [[1l50]], [[1l51]], [[1l52]], [[1l53]], [[1l54]], [[1l55]], [[1l56]], [[1l57]], [[1l58]], [[1l59]], [[1l60]], [[1l61]], [[1l62]], [[1l63]], [[1l64]], [[1l65]], [[1l66]], [[1l67]], [[1l68]], [[1l69]], [[1l70]], [[1l71]], [[1l72]], [[1l73]], [[1l74]], [[1l75]], [[1l76]], [[1l17]], [[1l18]], [[1l19]], [[1l20]], [[1l21]], [[1l22]], [[1l23]], [[1l24]], [[1l25]], [[1l26]], [[1l27]], [[1l28]], [[1l29]], [[1l30]], [[1l31]], [[1l32]], [[1l33]], [[1l34]], [[1l35]], [[3lzm]], [[1l01]], [[1l02]], [[1l03]], [[1l04]], [[1l05]], [[1l06]], [[1l07]], [[1l08]], [[1l09]], [[1l10]], [[1l11]], [[1l12]], [[1l13]], [[1l14]], [[1l15]], [[1l16]] – T4Lys (mutant) 
[[1c60]], [[1c61]], [[1c62]], [[1c63]], [[1c64]], [[1c65]], [[1c66]], [[1c67]], [[1c68]], [[1c69]], [[1c6a]], [[1c6b]], [[1c6c]], [[1c6d]], [[1c6e]], [[1c6f]], [[1c6g]], [[1c6h]], [[1c6i]], [[1c6j]], [[1c6k]], [[1c6l]], [[1c6m]], [[1c6n]], [[1c6p]], [[1c6q]], [[1c6t]] - T4Lys (mutant) + noble gas 
[[3ht6]], [[3ht7]], [[3ht8]], [[3ht9]], [[3htb]], [[3hu8]], [[3huq]], [[3guj]], [[3guk]], [[3gul]], [[3gum]], [[3gun]], [[3guo]], [[3gup]], [[3dmx]], [[3dmz]], [[3dn0]], [[3dn1]], [[3dn2]], [[3dn3]], [[3dn4]], [[3dn6]], [[3dn8]], [[3dna]], [[2rb1]], [[2ray]], [[2raz]], [[2rb0]], [[2rb2]], [[2rbn]], [[2rbo]], [[2rbq]], [[2rbr]], [[2rbs]], [[2oty]],[[2otz]], [[1owy]], [[1owz]], [[1ov5]], [[1ov7]], [[1ovh]], [[1ovj]], [[1ovk]], [[1lgw]], [[1lgx]], [[1li2]], [[1li3]], [[1l83]], [[1l84]] – T4Lys (mutant) + benzene derivative 
[[3htd]], [[3htf]], [[3htg]], [[3hu9]], [[3hua]], [[3huk]], [[3hh3]], [[3hh4]], [[3hh5]], [[3hh6]], [[2rbp]], [[2ou0]], [[2f2q]], [[2f32]], [[2f47]], [[1xep]] – T4Lys (mutant) + inhibitor 
[[148l]] - T4Lys (mutant) + glucoside 
[[3d3d]], [[1d9u]] – lamLys + chitohexasaccharide 
[[1am7]] – lamLys - Enterobacteria phage λ 
[[2anv]], [[2anx]] – Lys (mutant)]] - Enterobacteria phage p22 
[[1xjt]], [[1xju]] - Lys - Enterobacteria phage p1 
[[1lba]] - T7Lys - Enterobacteria phage T7 

===Lys protein complex===

[[3m18]], [[3g3a]], [[3g3b]] - HEWL + Variable lymphocyte receptor – Marine lamprey 
[[3a67]], [[3a6b]], [[3a6c]], [[2yss]], [[2eiz]], [[2dqc]], [[2dqd]], [[2dqe]], [[2dqf]], [[2dqg]], [[2dqh]], [[2dqi]], [[2dqj]], [[1j1o]], [[1j1p]], [[1j1x]], [[1ic4]], [[1ic5]], [[1ic7]] – HEWL + mLys antibody HYHEL-10 (mutant) 
[[1xgp]], [[1xgq]], [[1xgr]], [[1xgt]], [[1xgu]] – HEWL + mLys antibody HYHEL-63 
[[3d9a]], [[2eks]], [[1ua6]], [[1c08]], [[3hfm]] – HEWL + mLys antibody HYHEL-10 
[[1uac]] - tuLys C + mLys antibody HYHEL-10 
[[1yqv]], [[2iff]] – HEWL + mLys antibody HYHEL-5 
[[1bql]] – BqLys + mLys antibody HYHEL-5 
[[1ndg]] – HEWL + mLys antibody HYHEL-8 
[[1ndm]] – HEWL + mLys antibody HYHEL-26 
[[1dqj]] - HEWL + mLys antibody HYHEL-63 
[[1nby]], [[1nbz]] – HEWL (mutant) + mLys antibody HYHEL-63 
[[1g7h]], [[1g7i]], [[1g7j]], [[1g7l]], [[1g7m]], [[1kip]], [[1kiq]], [[1kir]] – HEWL + mAnti-HEWL monoclonal antibody (mutant) 
[[1mlc]], [[1vfb]] - HEWL + mIGG1-κ D44.1 FAB 
[[1a2y]] - HEWL (mutant) + mIGG1-κ D1.3 FV 
[[1fdl]] - HEWL + mIGG1-κ D1.3 FAB 
[[1jhl]] – phLys + mIGG1-κ D11.15 FV 
[[1fbi]] – GfLys + mIGG1 F9.13.7 FAB 
[[2znw]], [[2znx]] – HEWL + hSCFV10 antibody 
[[1bvk]] - HEWL + hAnti Lys FV antibody 
[[1dzb]] – tuLys + mSCFV 1F9 
[[1zv5]], [[1zvh]], [[1zvy]], [[1zmy]], [[1ri8]], [[1rjc]], [[1xfp]], [[1jtp]], [[1jtt]], [[1jto]], [[1mel]] - HEWL + cAntibody heavy chain domain – camel 
[[1op9]] - hLys C + cAntibody heavy chain domain 
[[3otp]] – HEWL + EcProtease DO – ''Escherichia coli'' 
[[3f6z]] - HEWL + MLIC – ''Pseudomonas aeruginosa'' 
[[3eba]] – hLys C + hCABHUL6 
[[2qb0]], [[2qar]] – T4Lys/E80 TELSAM domain 
[[2i25]], [[2i26]] - HEWL +NsAntigen receptor PBLA8 variable domain – Nurse shark 
[[1sq2]], [[1t6v]] – HEWL +NsNew Antigen receptor variable domain 
[[1gpq]] – HEWL + EcInhibitor of Vertebrate Lys 
[[1aro]] – T7Lys + T7 RNA polymerase 

===Some Useful External Links===
[http://en.wikipedia.org/wiki/Lysozyme Lysozyme]

[http://en.wikipedia.org/wiki/Glycoside_hydrolase#Retaining_glycoside_hydrolases Retaining Glycoside Hydrolases]

===References===
<references/>

Hen Egg-White (HEW) Lysozyme

2011-03-31T01:15:01Z

Anne Goodling:

<applet load='aln_1H6M_to_1HEW_2.pdb' size='250' frame='true' align='right' caption=' Hen Egg White (HEW) Lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to the active site, PDBid 1HEW' scene='User:Judy_Voet/Lysozyme/Lysozyme1/16' />
Lysozyme was the first enzyme whose X-ray structure was determined <ref> PMID 5840126</ref><ref>Phillips, D. C. The hen egg white lysozyme molecule. Proc. Natl Acad. Sci. USA 57, 483-495 (1967)</ref>. This <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>scene </scene> shows Hen Egg White (HEW) lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to a cleft in the enzyme. David Phillips, who determined the structure in 1965, saw that the cleft was large enough to fit three more saccharide units. He therefore built a model extending the trisaccharide to a
<scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> that fits into the cleft, labeling the sugar subsites A-F<ref> coordinates of the model kindly provided by Louise Johnson</ref>. Alternately click on <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>trisaccharide</scene> and <scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> to turn the modeled portion of the hexasaccharide on and off.
The interesting thing about the model was that the only way that the hexasaccharide would fit into the cleft was if the 4th saccharide (in subsite D) was strained into a <scene name='User:Judy_Voet/Lysozyme/Half-chair/2'>half-chair conformation</scene>. This conformation is what would be necessary for the formation of an oxocarbenium ion (oxionium ion). When the model was studied, <scene name='User:Judy_Voet/Lysozyme/Glu_35/1'>Glu 35</scene> was found to be in an ideal location to act as a general acid catalyst, 3.34 Angstroms from the bridging oxygen between the 4th and 5th saccharide units. <scene name='User:Judy_Voet/Lysozyme/Asp_52/2'>Asp 52</scene> appeared to be too far away (2.69 angstroms) in the static lysozyme structure to have formed a covalent bond with C1 of the half-chair model in the D site, and no covalent intermediate had ever been detected, so Phillips proposed that it acted as an electrostatic stabilizer of the oxonium ion (referred to as The Phillips Mechanism).
<applet load='aln_1H6M_to_1HEW_2.pdb' size='250' frame='true' align='left' caption='NAG-2-deoxy-2-fluoro-glucosyl fluoride (NAG2FGlcF) bound to Glu35Gln HEW Lysozyme PDBid 1H6M' scene='User:Judy_Voet/Lysozyme/1h6m/3'/>

Then, in 2001, Stephen Withers published <scene name='User:Judy_Voet/Lysozyme/1h6m/3'>1H6M</scene>,<ref>PMID 11518970</ref> in which Glu 35 had been mutated to Gln to remove the general acid catalyst. The substrate contained NAG-2-fluoro-glucosyl fluoride (NAG2FGlcF). The fluoro group on C-1 does not require acid catalysis to be a good leaving group, and the remaining saccharide, in the absence of the acid necessary to catalyse the second step of the reaction, was demonstrated to form a <scene name='User:Judy_Voet/Lysozyme/Covalent/1'> covalent intermediate</scene>. In this <scene name='User:Judy_Voet/Lysozyme/Superposition/2'>superposition</scene> of the half chair model with 1HEW (greens) and the covalent intermediate in 1H6M (blues), note the relatively small motions of Asp 52 and C1 of the sugar ring in going from the model to the covalent intermediate. to observe the motion from the <scene name='User:Judy_Voet/Lysozyme/Asp52_halfchair/1'>half-chair</scene> to the <scene name='User:Judy_Voet/Lysozyme/Covalent/2'>covalent intermediate</scene> just toggle between the two green links.

== 3D Structures of Lysozyme ==

===Lys===

[[2x0a]], [[3iju]], [[3ijv]], [[3a8z]], [[2w1y]], [[2w1m]], [[2w1x]], [[2w1l]], [[3e3d]], [[3exd]], [[2zq3]], [[2zq4]], [[3b72]], [[3b6l]], [[2z12]], [[2z18]], [[2z19]], [[2vb1]], [[2hu3]], [[2hub]], [[2htx]], [[2hu1]], [[2yvb]], [[2epe]], [[2g4p]], [[2g4q]], [[2cgi]], [[2b5z]], [[2d4k]], [[2d91]], [[2f2n]], [[2fbb]], [[2c8o]], [[2c8p]], [[2a6u]], [[2aub]], [[2blx]], [[2bly]], [[2a7d]], [[2a7f]], [[1wtm]], [[1wtn]], [[1w6z]], [[1vdp]], [[1vdq]], [[1vds]], [[1vdt]], [[1ved]], [[1v7t]], [[1ps5]], [[2cds]], [[1lj3]], [[1lj4]], [[1lje]], [[1ljf]], [[1ljg]], [[1ljh]], [[1lji]], [[1ljj]], [[1ljk]], [[1jis]], [[1jit]], [[1jiy]], [[1jj0]], [[1jj1]], [[1jj3]], [[1iee]], [[1qio]], [[1f0w]], [[1f10]], [[1dpx]], [[1c10]], [[1qtk]], [[1lz8]], [[1lz9]], [[1bhz]], [[1bgi]], [[1bwh]], [[1bwi]], [[1bwj]], [[1bvx]], [[1hsw]], [[1hsx]], [[1lpi]], [[4lzt]], [[3lzt]], [[1aki]], [[1jpo]], [[1rfp]], [[193l]], [[194l]], [[5lym]], [[1lza]], [[3lyt]], [[4lyt]], [[5lyt]], [[6lyt]], [[2lzt]], [[1lzt]], [[1lzh]], [[2lzh]], [[7lyz]], [[1lyz]], [[2lyz]], [[3lyz]], [[4lyz]], [[5lyz]], [[6lyz]] - HEWL – chicken 
[[1xei]], [[1xej]], [[1xek]], [[1uco]], [[1lma]], [[4lym]] – HEWL low hydration 
[[1lsa]], [[1lsb]], [[1lsc]], [[1lsd]], [[1lse]], [[1lsf]], [[1lys]] – HEWL temperature influence 
[[2lym]], [[3lym]] – HEWL pressure influence 
[[132l]] – HEWL methylated 
[[1rcm]] – HEWL 3 S-S form 
[[2xbr]], [[2xbs]]- HEWL– Raman crystallography 
[[2zwb]], [[1io5]], [[1lzn]] - HEWL– Neutron 
[[1gxv]], [[1gxx]], [[1e8l]] - HEWL- NMR 
[[2hs7]], [[2hso]], [[2hs9]]- HEWL– Powder diffraction 
[[1ir7]], [[1ir8]], [[1ir9]], [[1ioq]], [[1ior]], [[1ios]], [[1iot]], [[1flq]], [[1flu]], [[1flw]], [[1fly]], [[1fn5]], [[1kxw]], [[1kxx]], [[1kxy]], [[1uia]], [[1uib]], [[1uic]], [[1uid]], [[1uie]], [[1uif]], [[1uig]], [[1uih]], [[1lsm]], [[1lsn]], [[1hel]], [[1hem]], [[1hen]], [[1heo]], [[1hep]], [[1heq]], [[1her]] – HEWL (mutant) 
[[1lyo]], [[2lyo]], [[3lyo]], [[4lyo]] – HEWL cross-linked 
[[1xft]] - tuLys – turkey - Powder diffraction 
[[1jse]], [[1tew]], [[135l]], [[2lz2]], [[1lz2]] – tuLys 
[[3lz2]] – tuLys - Laue 
[[3ab6]] – Lys + NAG3 – Hard clam 
[[2x8r]] – Lys GH25 – ''Aspergillus fumigatus'' 
[[3mgw]] – Lys G – Atlantic salmon 
[[3gxk]], [[3gxr]] – Lys G + NAG – Atlantic cod 
[[2fbd]] – HfLys 1 
[[3cb7]] – HfLys 2 
[[2zij]], [[2zik]], [[2zil]], [[2nwd]], [[1iwt]], [[1iwu]], [[1iwv]], [[1iww]], [[1iwx]], [[1iwy]], [[1iwz]], [[1jwr]], [[1jsf]], [[1rex]], [[1lz1]] – hLys – human 
[[1w08]], [[1ix0]], [[1ioc]], [[1ip1]], [[1ip2]], [[1ip3]], [[1ip4]], [[1ip5]], [[1ip6]], [[1ip7]], [[1qsw]], [[1gev]], [[1gez]], [[1gf0]], [[1gf3]], [[1gf4]], [[1gf5]], [[1gf6]], [[1gf7]], [[1i1z]], [[1i20]], [[1i22]], [[1gfr]], [[1gft]], [[1gfu]], [[1gfv]], [[1gf8]], [[1gf9]], [[1gfa]], [[1gfe]], [[1gfg]], [[1gfh]], [[1gfj]], [[1gfk]], [[1inu]], [[1gdx]], [[1ge0]], [[1ge1]], [[1ge2]], [[1ge3]], [[1ge4]], [[1gdw]], [[1gaz]], [[1gb0]], [[1gb2]], [[1gb3]], [[1gb5]], [[1gb6]], [[1gb7]], [[1gb8]], [[1gb9]], [[1gbo]], [[1gbw]], [[1gbx]], [[1gby]], [[1gbz]], [[1gay]], [[1eq4]], [[1eq5]], [[1eqe]], [[1c7p]], [[1di3]], [[1di4]], [[1di5]], [[1c43]], [[1c45]], [[1c46]], [[1ckg]], [[1cj6]], [[1cj7]], [[1cj8]], [[1cj9]], [[1ckc]], [[1ckd]], [[1ckf]], [[1ckh]], [[1b5z]], [[1b70]], [[1b7q]], [[1b7r]], [[1b7s]], [[1b7l]], [[1b7m]], [[1b7n]], [[1b7p]], [[1b5u]], [[1b5v]], [[1b5w]], [[1b5x]], [[1b5y]], [[1bb3]], [[1bb4]], [[2bqa]], [[2bqb]], [[2bqc]], [[2bqd]], [[2bqe]], [[2bqf]], [[2bqg]], [[2bqh]], [[2bqi]], [[2bqj]], [[2bqk]], [[2bql]], [[2bqm]], [[2bqn]], [[2bqo]], [[2mea]], [[2meb]], [[2mec]], [[2med]], [[2mee]], [[2mef]], [[2meg]], [[2meh]], [[2mei]], [[1wqm]], [[1wqn]], [[1wqo]], [[1wqp]], [[1wqq]], [[1wqr]], [[2heb]], [[2hea]], [[2hec]], [[2hed]], [[2hee]], [[2hef]], [[1jka]], [[1jkb]], [[1jkc]], [[1jkd]], [[1loz]], [[1lyy]], [[1oua]], [[1oub]], [[1ouc]], [[1oud]], [[1oue]], [[1ouf]], [[1oug]], [[1ouh]], [[1oui]], [[1ouj]], [[207l]], [[208l ]], [[1yam]], [[1yan]], [[1yao]], [[1yap]], [[1yaq]], [[1lmt]], [[1lhh]], [[1lhi]], [[1lhj]], [[1lhk]], [[1lhl]], [[133l]], [[134l]], [[1lz4]], [[1lz5]], [[1lz6]], [[1laa]], [[1tay]], [[1tby]], [[1tcy]], [[1tdy]], [[2lhm]], [[3lhm]] – hLys (mutant) 
[[1iy3]], [[1iy4]] – hLys - NMR 
[[2z2f]] – Lys – Bovine 
[[2cwi]], [[1el1]], [[1qqy]] – dLys - dog 
[[2z2e]] – dLys (mutant) 
[[1i56]] – dLys – NMR 
[[2dqa]] – Lys – ''Tapes japonica'' 
[[2gv0]] – Lys – Soft-shelled turtle 
[[1ivm]] – mLys M – NMR – mouse 
[[1jfx]] – Lys – ''Streptomyces coelicolor'' 
[[1gd6]] – Lys – ''Bombyx mori'' 
[[1jug]] – Lys – Echidna 
[[1dkj]] – BqLys – Bobwhite quail 
[[2ihl]] – Lys – Japanese quail 
[[1gbs]] – BsLys – Black swan 
[[1lmn]] – RtLys – Rainbow trout 
[[2eql]] – Lys – horse 
[[1ghl]] – phLys – pheasant 
[[1hhl]] – GfLys – Guinea fowl 
[[1lhm]] – Lys (mutant) – yeast 

===Lys small molecules complexes===

[[3fe0]], [[2d4i]], [[2d4j]], [[1v7s]] - HEWL+ D2O 
[[3m3u]] – HEWL Trp fluorescence 
[[2xjw]] - HEWL + CO 
[[1hf4]], [[1lks]] – HEWL + NO3 
[[3a34]], [[3ems]] - HEWL + arginine 
[[2xth]] – cLys + inhibitor K2PtBr6 
[[3a90]], [[3a91]], [[3a92]], [[3a93]], [[3a94]], [[3a95]], [[3a96]], [[3kam]], [[2pc2]], [[2bpu]], [[1t3p]], [[1h87]] – HEWL + rare earth 
[[2d6b]], [[2hg0]], [[1vat]], [[1gwd]], [[1b2k]], [[1lkr]], [[1azf]], [[8lyz]]- HEWL+ halogen 
[[1vat]] - HEWL + Xe 
[[1n4f]] - HEWL + As 
[[2i6z]] - HEWL + Pt drug 
[[2zyp]] - HEWL + poly (allyl amine) 
[[2f30]], [[2f4a]] – HEWL + urea derivative 
[[2f4g]], [[1ykx]], [[1yky]], [[1ykz]], [[1yl0]], [[1yl1]], [[1z55]] - HEWL + alcohol 
[[1dpw]] – HEWL + MPD 
[[1lcn]] – HEWL + SCN 
[[2zxs]] - HEWL with glycine-amide 
[[2h9j]], [[2h9k]], [[1yik]], [[1yil]] - HEWL + cyclam derivative 
[[1b0d]] – HEWL + p-toluene-sulfonate 
[[2q0m]] - HEWL + tricarbonylmanganese 
[[2war]] – HEWL (mutant) + chitopentaose 
[[2h5z]] – HfLys 1 + chitotetraose – House fly 
[[1hnl]] – hLys + glutathione 
[[1dkk]] – BqLys + NO3 

===Lys complex with glucoside===

[[3a3q]] – HEWL (mutant) + NAG 
[[1sf4]], [[1sf6]], [[1sf7]], [[1sfb]], [[1sfg]], [[1ja2]], [[1ja4]], [[1ja6]], [[1ja7]] – HEWL + NAG oligosaccharide – Powder diffraction 
[[1ubz]], [[1d6p]], [[1d6q]], [[1bb5]] – hLys (mutant) + glycoside 
[[1uc0]], [[1re2]], [[1rem]], [[1rey]], [[1rez]], [[1lzr]], [[1lzs]] - hLys + glycoside 
[[1ljn]], [[1jef]], [[1lzy]] – tuLys + glycoside 
[[1h6m]], [[1at5]], [[1at6]], [[1lzb]], [[1lzc]], [[1lzd]], [[1lze]], [[1lzg]], [[1hew ]]– HEWL + glycoside 
[[1lsy]], [[1lsz]] - HEWL (mutant) + glycoside 
[[1bb6]], [[1bb7]] – RtLys + glycoside 
[[1lmc]] – RtLys + bulgecin 
[[1lmo]], [[1lmp]], [[1lmq]] – RtLys + glucoside 
[[1lsp]] – BsLys + bulgecin 
[[153l]], [[154l]] – Lys +glucoside – goose 

===Phage Lys===

[[2oe4]], [[2oe7]], [[2oe9]], [[2oea]], [[1swz]], [[1cx6]], [[1qtc]], [[1qtd]], [[1qth]], [[1qsb]], [[1qs5]], [[1qs9]], [[1qtb]], [[256l]], [[206l]], [[167l]], [[168l]], [[169l]], [[170l]], [[171l]], [[172l]], [[173l]], [[174l]], [[175l]], [[176l]], [[177l]], [[178l]], [[181l]], [[182l]], [[183l]], [[184l]], [[185l]], [[186l]], [[187l]], [[188l]], [[1nhb]], [[137l]], [[216l]], [[152l]], [[149l]], [[150l]], [[151l]], [[1lyd]], [[2lzm]] - T4Lys – Enterobacteria phage T4 
[[138l]] – T4Lys cross-linked 
[[4lzm]], [[5lzm]], [[6lzm]], [[7lzm]] – T4Lys ionic strength 
[[3l2x]], [[3k2r]], [[3g3v]], [[3g3w]], [[3g3x]], [[2q9d]], [[2q9e]], [[2igc]], [[2ntg]], [[2nth]], [[2ou8]], [[2ou9]], [[1zur]], [[1zwn]], [[1zyt]], [[2cuu]], [[2a4t]] – T4Lys (mutant) spin labeled 
[[3l64]], [[3hwl]], [[3jr6]], [[3gui]], [[3c7w]], [[3c7y]], [[3c7z]], [[3c80]], [[3c81]], [[3c82]], [[3c83]], [[3c8q]], [[3c8r]], [[3c8s]], [[3cdo]], [[3cdq]], [[3cdr]], [[3cdt]], [[3cdv]], [[3f8v]], [[3f9l]], [[3fa0]], [[3fad]], [[3fi5]], [[3dke]], [[3dmv]], [[2o4w]], [[2o79]], [[2o7a]], [[2huk]], [[2hul]], [[2hum]], [[2b7x]], [[2b6t]], [[2b6w]], [[2b6x]], [[2b6y]], [[2b6z]], [[2b70]], [[2b72]], [[2b73]], [[2b74]], [[2b75]], [[1sx7]], [[1swy]], [[1sx2]], [[1t6h]], [[1ssw]], [[1ssy]], [[1t8f]], [[1t8g]], [[1t8a]], [[1t97]], [[1p56]], [[1p5c]], [[1p2l]], [[1p2r]], [[1p36]], [[1p37]], [[1p3n]], [[1p46]], [[1p64]], [[1p6y]], [[1p7s]], [[1pqd]], [[1pqi]], [[1pqj]], [[1pqk]], [[1pqm]], [[1pqo]], [[1oyu]], [[1ks3]], [[1kw5]], [[1kw7]], [[1ky0]], [[1ky1]], [[1l0j]], [[1l0k]], [[1lw9]], [[1lwg]], [[1lwk]], [[1lpy]], [[1llh]], [[1lgu]], [[1li6]], [[1jtm]], [[1jtn]], [[1jqu]], [[1kni]], [[1g06]], [[1g07]], [[1g0g]], [[1g0j]], [[1g0k]], [[1g0l]], [[1g0m]], [[1g0p]], [[1g0q]], [[1g1v]], [[1g1w]], [[1i6s]], [[257l]], [[258l]], [[260l]], [[1epy]], [[1b6i]], [[1cu6]], [[1d9w]], [[1ctw]], [[1cu0]], [[1cu2]], [[1cu3]], [[1cu5]], [[1cv1]], [[1cv4]], [[1cv5]], [[1cv6]], [[1cvk]], [[1cx7]], [[1d2w]], [[1d2y]], [[1d3f]], [[1d3j]], [[1d3m]], [[1d3n]], [[1cv3]], [[1qt3]], [[1qt4]], [[1qt5]], [[1qt6]], [[1qt7]], [[1qt8]], [[1qtv]], [[1qtz]], [[1qud]], [[1qug]], [[1quh]], [[1quo]], [[1qsq]], [[261l]], [[262l]], [[259l]], [[220l]], [[222l]], [[223l]], [[225l]], [[226l]], [[227l]], [[228l]], [[229l]], [[235l]], [[236l]], [[237l]], [[238l]], [[239l]], [[240l]], [[241l]], [[242l]], [[243l]], [[244l]], [[245l]], [[246l]], [[247l]], [[248l]], [[249l]], [[250l]], [[251l]], [[252l]], [[253l]], [[254l]], [[255l]], [[230l]], [[231l]], [[232l]], [[233l]], [[234l]], [[209l]], [[210l]], [[211l]], [[212l]], [[213l]], [[214l]], [[215l]], [[218l]], [[219l]], [[180l]], [[195l]], [[196l]], [[197l]], [[198l]], [[199l]], [[200l]], [[190l]], [[191l]], [[192l]], [[189l]], [[155l]], [[156l]], [[157l]], [[158l]], [[159l]], [[160l]], [[161l]], [[162l]], [[163l]], [[164l]], [[165l]], [[166l]], [[129l]], [[130l]], [[131l]], [[140l]], [[141l]], [[142l]], [[143l]], [[144l]], [[145l]], [[146l]], [[147l]], [[201l]], [[205l]], [[221l]], [[224l]], [[102l]], [[103l]], [[104l]], [[107l]], [[108l]], [[109l]], [[110l]], [[111l]], [[112l]], [[113l]], [[114l]], [[115l]], [[118l]], [[119l]], [[120l]], [[122l]], [[123l]], [[125l]], [[126l]], [[127l]], [[128l]], [[1dya]], [[1dyb]], [[1dyc]], [[1dyd]], [[1dye]], [[1dyf]], [[1dyg]], [[1l00]], [[1l85]], [[1l86]], [[1l87]], [[1l88]], [[1l89]], [[1l90]], [[1l91]], [[1l92]], [[1l93]], [[1l94]], [[1l95]], [[1l96]], [[1l97]], [[1l98]], [[1l99]], [[1lye]], [[1lyf]], [[1lyg]], [[1lyh]], [[1lyi]], [[1lyj]], [[217l]], [[1tla]], [[1l77]], [[1l79]], [[1l80]], [[1l81]], [[1l82]], [[2l78]], [[1l36]], [[1l37]], [[1l38]], [[1l39]], [[1l40]], [[1l41]], [[1l42]], [[1l43]], [[1l44]], [[1l45]], [[1l46]], [[1l47]], [[1l48]], [[1l49]], [[1l50]], [[1l51]], [[1l52]], [[1l53]], [[1l54]], [[1l55]], [[1l56]], [[1l57]], [[1l58]], [[1l59]], [[1l60]], [[1l61]], [[1l62]], [[1l63]], [[1l64]], [[1l65]], [[1l66]], [[1l67]], [[1l68]], [[1l69]], [[1l70]], [[1l71]], [[1l72]], [[1l73]], [[1l74]], [[1l75]], [[1l76]], [[1l17]], [[1l18]], [[1l19]], [[1l20]], [[1l21]], [[1l22]], [[1l23]], [[1l24]], [[1l25]], [[1l26]], [[1l27]], [[1l28]], [[1l29]], [[1l30]], [[1l31]], [[1l32]], [[1l33]], [[1l34]], [[1l35]], [[3lzm]], [[1l01]], [[1l02]], [[1l03]], [[1l04]], [[1l05]], [[1l06]], [[1l07]], [[1l08]], [[1l09]], [[1l10]], [[1l11]], [[1l12]], [[1l13]], [[1l14]], [[1l15]], [[1l16]] – T4Lys (mutant) 
[[1c60]], [[1c61]], [[1c62]], [[1c63]], [[1c64]], [[1c65]], [[1c66]], [[1c67]], [[1c68]], [[1c69]], [[1c6a]], [[1c6b]], [[1c6c]], [[1c6d]], [[1c6e]], [[1c6f]], [[1c6g]], [[1c6h]], [[1c6i]], [[1c6j]], [[1c6k]], [[1c6l]], [[1c6m]], [[1c6n]], [[1c6p]], [[1c6q]], [[1c6t]] - T4Lys (mutant) + noble gas 
[[3ht6]], [[3ht7]], [[3ht8]], [[3ht9]], [[3htb]], [[3hu8]], [[3huq]], [[3guj]], [[3guk]], [[3gul]], [[3gum]], [[3gun]], [[3guo]], [[3gup]], [[3dmx]], [[3dmz]], [[3dn0]], [[3dn1]], [[3dn2]], [[3dn3]], [[3dn4]], [[3dn6]], [[3dn8]], [[3dna]], [[2rb1]], [[2ray]], [[2raz]], [[2rb0]], [[2rb2]], [[2rbn]], [[2rbo]], [[2rbq]], [[2rbr]], [[2rbs]], [[2oty]],[[2otz]], [[1owy]], [[1owz]], [[1ov5]], [[1ov7]], [[1ovh]], [[1ovj]], [[1ovk]], [[1lgw]], [[1lgx]], [[1li2]], [[1li3]], [[1l83]], [[1l84]] – T4Lys (mutant) + benzene derivative 
[[3htd]], [[3htf]], [[3htg]], [[3hu9]], [[3hua]], [[3huk]], [[3hh3]], [[3hh4]], [[3hh5]], [[3hh6]], [[2rbp]], [[2ou0]], [[2f2q]], [[2f32]], [[2f47]], [[1xep]] – T4Lys (mutant) + inhibitor 
[[148l]] - T4Lys (mutant) + glucoside 
[[3d3d]], [[1d9u]] – lamLys + chitohexasaccharide 
[[1am7]] – lamLys - Enterobacteria phage λ 
[[2anv]], [[2anx]] – Lys (mutant)]] - Enterobacteria phage p22 
[[1xjt]], [[1xju]] - Lys - Enterobacteria phage p1 
[[1lba]] - T7Lys - Enterobacteria phage T7 

===Lys protein complex===

[[3m18]], [[3g3a]], [[3g3b]] - HEWL + Variable lymphocyte receptor – Marine lamprey 
[[3a67]], [[3a6b]], [[3a6c]], [[2yss]], [[2eiz]], [[2dqc]], [[2dqd]], [[2dqe]], [[2dqf]], [[2dqg]], [[2dqh]], [[2dqi]], [[2dqj]], [[1j1o]], [[1j1p]], [[1j1x]], [[1ic4]], [[1ic5]], [[1ic7]] – HEWL + mLys antibody HYHEL-10 (mutant) 
[[1xgp]], [[1xgq]], [[1xgr]], [[1xgt]], [[1xgu]] – HEWL + mLys antibody HYHEL-63 
[[3d9a]], [[2eks]], [[1ua6]], [[1c08]], [[3hfm]] – HEWL + mLys antibody HYHEL-10 
[[1uac]] - tuLys C + mLys antibody HYHEL-10 
[[1yqv]], [[2iff]] – HEWL + mLys antibody HYHEL-5 
[[1bql]] – BqLys + mLys antibody HYHEL-5 
[[1ndg]] – HEWL + mLys antibody HYHEL-8 
[[1ndm]] – HEWL + mLys antibody HYHEL-26 
[[1dqj]] - HEWL + mLys antibody HYHEL-63 
[[1nby]], [[1nbz]] – HEWL (mutant) + mLys antibody HYHEL-63 
[[1g7h]], [[1g7i]], [[1g7j]], [[1g7l]], [[1g7m]], [[1kip]], [[1kiq]], [[1kir]] – HEWL + mAnti-HEWL monoclonal antibody (mutant) 
[[1mlc]], [[1vfb]] - HEWL + mIGG1-κ D44.1 FAB 
[[1a2y]] - HEWL (mutant) + mIGG1-κ D1.3 FV 
[[1fdl]] - HEWL + mIGG1-κ D1.3 FAB 
[[1jhl]] – phLys + mIGG1-κ D11.15 FV 
[[1fbi]] – GfLys + mIGG1 F9.13.7 FAB 
[[2znw]], [[2znx]] – HEWL + hSCFV10 antibody 
[[1bvk]] - HEWL + hAnti Lys FV antibody 
[[1dzb]] – tuLys + mSCFV 1F9 
[[1zv5]], [[1zvh]], [[1zvy]], [[1zmy]], [[1ri8]], [[1rjc]], [[1xfp]], [[1jtp]], [[1jtt]], [[1jto]], [[1mel]] - HEWL + cAntibody heavy chain domain – camel 
[[1op9]] - hLys C + cAntibody heavy chain domain 
[[3otp]] – HEWL + EcProtease DO – ''Escherichia coli'' 
[[3f6z]] - HEWL + MLIC – ''Pseudomonas aeruginosa'' 
[[3eba]] – hLys C + hCABHUL6 
[[2qb0]], [[2qar]] – T4Lys/E80 TELSAM domain 
[[2i25]], [[2i26]] - HEWL +NsAntigen receptor PBLA8 variable domain – Nurse shark 
[[1sq2]], [[1t6v]] – HEWL +NsNew Antigen receptor variable domain 
[[1gpq]] – HEWL + EcInhibitor of Vertebrate Lys 
[[1aro]] – T7Lys + T7 RNA polymerase 

===Some Useful External Links===
[http://en.wikipedia.org/wiki/Lysozyme Lysozyme]

[http://en.wikipedia.org/wiki/Glycoside_hydrolase#Retaining_glycoside_hydrolases Retaining Glycoside Hydrolases]

===References===
<references/>

Hen Egg-White (HEW) Lysozyme

2011-03-31T01:12:07Z

Anne Goodling:

<applet load='aln_1H6M_to_1HEW_2.pdb' size='200' frame='true' align='right' caption=' Hen Egg White (HEW) Lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to the active site, PDBid 1HEW' scene='User:Judy_Voet/Lysozyme/Lysozyme1/16' />
Lysozyme was the first enzyme whose X-ray structure was determined <ref> PMID 5840126</ref><ref>Phillips, D. C. The hen egg white lysozyme molecule. Proc. Natl Acad. Sci. USA 57, 483-495 (1967)</ref>. This <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>scene </scene> shows Hen Egg White (HEW) lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to a cleft in the enzyme. David Phillips, who determined the structure in 1965, saw that the cleft was large enough to fit three more saccharide units. He therefore built a model extending the trisaccharide to a
<scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> that fits into the cleft, labeling the sugar subsites A-F<ref> coordinates of the model kindly provided by Louise Johnson</ref>. Alternately click on <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>trisaccharide</scene> and <scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> to turn the modeled portion of the hexasaccharide on and off.
The interesting thing about the model was that the only way that the hexasaccharide would fit into the cleft was if the 4th saccharide (in subsite D) was strained into a <scene name='User:Judy_Voet/Lysozyme/Half-chair/2'>half-chair conformation</scene>. This conformation is what would be necessary for the formation of an oxocarbenium ion (oxionium ion). When the model was studied, <scene name='User:Judy_Voet/Lysozyme/Glu_35/1'>Glu 35</scene> was found to be in an ideal location to act as a general acid catalyst, 3.34 Angstroms from the bridging oxygen between the 4th and 5th saccharide units. <scene name='User:Judy_Voet/Lysozyme/Asp_52/2'>Asp 52</scene> appeared to be too far away (2.69 angstroms) in the static lysozyme structure to have formed a covalent bond with C1 of the half-chair model in the D site, and no covalent intermediate had ever been detected, so Phillips proposed that it acted as an electrostatic stabilizer of the oxonium ion (referred to as The Phillips Mechanism).
<applet load='aln_1H6M_to_1HEW_2.pdb' size='200' frame='true' align='left' caption='NAG-2-deoxy-2-fluoro-glucosyl fluoride (NAG2FGlcF) bound to Glu35Gln HEW Lysozyme PDBid 1H6M' scene='User:Judy_Voet/Lysozyme/1h6m/3'/>

Then, in 2001, Stephen Withers published <scene name='User:Judy_Voet/Lysozyme/1h6m/3'>1H6M</scene>,<ref>PMID 11518970</ref> in which Glu 35 had been mutated to Gln to remove the general acid catalyst. The substrate contained NAG-2-fluoro-glucosyl fluoride (NAG2FGlcF). The fluoro group on C-1 does not require acid catalysis to be a good leaving group, and the remaining saccharide, in the absence of the acid necessary to catalyse the second step of the reaction, was demonstrated to form a <scene name='User:Judy_Voet/Lysozyme/Covalent/1'> covalent intermediate</scene>. In this <scene name='User:Judy_Voet/Lysozyme/Superposition/2'>superposition</scene> of the half chair model with 1HEW (greens) and the covalent intermediate in 1H6M (blues), note the relatively small motions of Asp 52 and C1 of the sugar ring in going from the model to the covalent intermediate. to observe the motion from the <scene name='User:Judy_Voet/Lysozyme/Asp52_halfchair/1'>half-chair</scene> to the <scene name='User:Judy_Voet/Lysozyme/Covalent/2'>covalent intermediate</scene> just toggle between the two green links.

== 3D Structures of Lysozyme ==

===Lys===

[[2x0a]], [[3iju]], [[3ijv]], [[3a8z]], [[2w1y]], [[2w1m]], [[2w1x]], [[2w1l]], [[3e3d]], [[3exd]], [[2zq3]], [[2zq4]], [[3b72]], [[3b6l]], [[2z12]], [[2z18]], [[2z19]], [[2vb1]], [[2hu3]], [[2hub]], [[2htx]], [[2hu1]], [[2yvb]], [[2epe]], [[2g4p]], [[2g4q]], [[2cgi]], [[2b5z]], [[2d4k]], [[2d91]], [[2f2n]], [[2fbb]], [[2c8o]], [[2c8p]], [[2a6u]], [[2aub]], [[2blx]], [[2bly]], [[2a7d]], [[2a7f]], [[1wtm]], [[1wtn]], [[1w6z]], [[1vdp]], [[1vdq]], [[1vds]], [[1vdt]], [[1ved]], [[1v7t]], [[1ps5]], [[2cds]], [[1lj3]], [[1lj4]], [[1lje]], [[1ljf]], [[1ljg]], [[1ljh]], [[1lji]], [[1ljj]], [[1ljk]], [[1jis]], [[1jit]], [[1jiy]], [[1jj0]], [[1jj1]], [[1jj3]], [[1iee]], [[1qio]], [[1f0w]], [[1f10]], [[1dpx]], [[1c10]], [[1qtk]], [[1lz8]], [[1lz9]], [[1bhz]], [[1bgi]], [[1bwh]], [[1bwi]], [[1bwj]], [[1bvx]], [[1hsw]], [[1hsx]], [[1lpi]], [[4lzt]], [[3lzt]], [[1aki]], [[1jpo]], [[1rfp]], [[193l]], [[194l]], [[5lym]], [[1lza]], [[3lyt]], [[4lyt]], [[5lyt]], [[6lyt]], [[2lzt]], [[1lzt]], [[1lzh]], [[2lzh]], [[7lyz]], [[1lyz]], [[2lyz]], [[3lyz]], [[4lyz]], [[5lyz]], [[6lyz]] - HEWL – chicken 
[[1xei]], [[1xej]], [[1xek]], [[1uco]], [[1lma]], [[4lym]] – HEWL low hydration 
[[1lsa]], [[1lsb]], [[1lsc]], [[1lsd]], [[1lse]], [[1lsf]], [[1lys]] – HEWL temperature influence 
[[2lym]], [[3lym]] – HEWL pressure influence 
[[132l]] – HEWL methylated 
[[1rcm]] – HEWL 3 S-S form 
[[2xbr]], [[2xbs]]- HEWL– Raman crystallography 
[[2zwb]], [[1io5]], [[1lzn]] - HEWL– Neutron 
[[1gxv]], [[1gxx]], [[1e8l]] - HEWL- NMR 
[[2hs7]], [[2hso]], [[2hs9]]- HEWL– Powder diffraction 
[[1ir7]], [[1ir8]], [[1ir9]], [[1ioq]], [[1ior]], [[1ios]], [[1iot]], [[1flq]], [[1flu]], [[1flw]], [[1fly]], [[1fn5]], [[1kxw]], [[1kxx]], [[1kxy]], [[1uia]], [[1uib]], [[1uic]], [[1uid]], [[1uie]], [[1uif]], [[1uig]], [[1uih]], [[1lsm]], [[1lsn]], [[1hel]], [[1hem]], [[1hen]], [[1heo]], [[1hep]], [[1heq]], [[1her]] – HEWL (mutant) 
[[1lyo]], [[2lyo]], [[3lyo]], [[4lyo]] – HEWL cross-linked 
[[1xft]] - tuLys – turkey - Powder diffraction 
[[1jse]], [[1tew]], [[135l]], [[2lz2]], [[1lz2]] – tuLys 
[[3lz2]] – tuLys - Laue 
[[3ab6]] – Lys + NAG3 – Hard clam 
[[2x8r]] – Lys GH25 – ''Aspergillus fumigatus'' 
[[3mgw]] – Lys G – Atlantic salmon 
[[3gxk]], [[3gxr]] – Lys G + NAG – Atlantic cod 
[[2fbd]] – HfLys 1 
[[3cb7]] – HfLys 2 
[[2zij]], [[2zik]], [[2zil]], [[2nwd]], [[1iwt]], [[1iwu]], [[1iwv]], [[1iww]], [[1iwx]], [[1iwy]], [[1iwz]], [[1jwr]], [[1jsf]], [[1rex]], [[1lz1]] – hLys – human 
[[1w08]], [[1ix0]], [[1ioc]], [[1ip1]], [[1ip2]], [[1ip3]], [[1ip4]], [[1ip5]], [[1ip6]], [[1ip7]], [[1qsw]], [[1gev]], [[1gez]], [[1gf0]], [[1gf3]], [[1gf4]], [[1gf5]], [[1gf6]], [[1gf7]], [[1i1z]], [[1i20]], [[1i22]], [[1gfr]], [[1gft]], [[1gfu]], [[1gfv]], [[1gf8]], [[1gf9]], [[1gfa]], [[1gfe]], [[1gfg]], [[1gfh]], [[1gfj]], [[1gfk]], [[1inu]], [[1gdx]], [[1ge0]], [[1ge1]], [[1ge2]], [[1ge3]], [[1ge4]], [[1gdw]], [[1gaz]], [[1gb0]], [[1gb2]], [[1gb3]], [[1gb5]], [[1gb6]], [[1gb7]], [[1gb8]], [[1gb9]], [[1gbo]], [[1gbw]], [[1gbx]], [[1gby]], [[1gbz]], [[1gay]], [[1eq4]], [[1eq5]], [[1eqe]], [[1c7p]], [[1di3]], [[1di4]], [[1di5]], [[1c43]], [[1c45]], [[1c46]], [[1ckg]], [[1cj6]], [[1cj7]], [[1cj8]], [[1cj9]], [[1ckc]], [[1ckd]], [[1ckf]], [[1ckh]], [[1b5z]], [[1b70]], [[1b7q]], [[1b7r]], [[1b7s]], [[1b7l]], [[1b7m]], [[1b7n]], [[1b7p]], [[1b5u]], [[1b5v]], [[1b5w]], [[1b5x]], [[1b5y]], [[1bb3]], [[1bb4]], [[2bqa]], [[2bqb]], [[2bqc]], [[2bqd]], [[2bqe]], [[2bqf]], [[2bqg]], [[2bqh]], [[2bqi]], [[2bqj]], [[2bqk]], [[2bql]], [[2bqm]], [[2bqn]], [[2bqo]], [[2mea]], [[2meb]], [[2mec]], [[2med]], [[2mee]], [[2mef]], [[2meg]], [[2meh]], [[2mei]], [[1wqm]], [[1wqn]], [[1wqo]], [[1wqp]], [[1wqq]], [[1wqr]], [[2heb]], [[2hea]], [[2hec]], [[2hed]], [[2hee]], [[2hef]], [[1jka]], [[1jkb]], [[1jkc]], [[1jkd]], [[1loz]], [[1lyy]], [[1oua]], [[1oub]], [[1ouc]], [[1oud]], [[1oue]], [[1ouf]], [[1oug]], [[1ouh]], [[1oui]], [[1ouj]], [[207l]], [[208l ]], [[1yam]], [[1yan]], [[1yao]], [[1yap]], [[1yaq]], [[1lmt]], [[1lhh]], [[1lhi]], [[1lhj]], [[1lhk]], [[1lhl]], [[133l]], [[134l]], [[1lz4]], [[1lz5]], [[1lz6]], [[1laa]], [[1tay]], [[1tby]], [[1tcy]], [[1tdy]], [[2lhm]], [[3lhm]] – hLys (mutant) 
[[1iy3]], [[1iy4]] – hLys - NMR 
[[2z2f]] – Lys – Bovine 
[[2cwi]], [[1el1]], [[1qqy]] – dLys - dog 
[[2z2e]] – dLys (mutant) 
[[1i56]] – dLys – NMR 
[[2dqa]] – Lys – ''Tapes japonica'' 
[[2gv0]] – Lys – Soft-shelled turtle 
[[1ivm]] – mLys M – NMR – mouse 
[[1jfx]] – Lys – ''Streptomyces coelicolor'' 
[[1gd6]] – Lys – ''Bombyx mori'' 
[[1jug]] – Lys – Echidna 
[[1dkj]] – BqLys – Bobwhite quail 
[[2ihl]] – Lys – Japanese quail 
[[1gbs]] – BsLys – Black swan 
[[1lmn]] – RtLys – Rainbow trout 
[[2eql]] – Lys – horse 
[[1ghl]] – phLys – pheasant 
[[1hhl]] – GfLys – Guinea fowl 
[[1lhm]] – Lys (mutant) – yeast 

===Lys small molecules complexes===

[[3fe0]], [[2d4i]], [[2d4j]], [[1v7s]] - HEWL+ D2O 
[[3m3u]] – HEWL Trp fluorescence 
[[2xjw]] - HEWL + CO 
[[1hf4]], [[1lks]] – HEWL + NO3 
[[3a34]], [[3ems]] - HEWL + arginine 
[[2xth]] – cLys + inhibitor K2PtBr6 
[[3a90]], [[3a91]], [[3a92]], [[3a93]], [[3a94]], [[3a95]], [[3a96]], [[3kam]], [[2pc2]], [[2bpu]], [[1t3p]], [[1h87]] – HEWL + rare earth 
[[2d6b]], [[2hg0]], [[1vat]], [[1gwd]], [[1b2k]], [[1lkr]], [[1azf]], [[8lyz]]- HEWL+ halogen 
[[1vat]] - HEWL + Xe 
[[1n4f]] - HEWL + As 
[[2i6z]] - HEWL + Pt drug 
[[2zyp]] - HEWL + poly (allyl amine) 
[[2f30]], [[2f4a]] – HEWL + urea derivative 
[[2f4g]], [[1ykx]], [[1yky]], [[1ykz]], [[1yl0]], [[1yl1]], [[1z55]] - HEWL + alcohol 
[[1dpw]] – HEWL + MPD 
[[1lcn]] – HEWL + SCN 
[[2zxs]] - HEWL with glycine-amide 
[[2h9j]], [[2h9k]], [[1yik]], [[1yil]] - HEWL + cyclam derivative 
[[1b0d]] – HEWL + p-toluene-sulfonate 
[[2q0m]] - HEWL + tricarbonylmanganese 
[[2war]] – HEWL (mutant) + chitopentaose 
[[2h5z]] – HfLys 1 + chitotetraose – House fly 
[[1hnl]] – hLys + glutathione 
[[1dkk]] – BqLys + NO3 

===Lys complex with glucoside===

[[3a3q]] – HEWL (mutant) + NAG 
[[1sf4]], [[1sf6]], [[1sf7]], [[1sfb]], [[1sfg]], [[1ja2]], [[1ja4]], [[1ja6]], [[1ja7]] – HEWL + NAG oligosaccharide – Powder diffraction 
[[1ubz]], [[1d6p]], [[1d6q]], [[1bb5]] – hLys (mutant) + glycoside 
[[1uc0]], [[1re2]], [[1rem]], [[1rey]], [[1rez]], [[1lzr]], [[1lzs]] - hLys + glycoside 
[[1ljn]], [[1jef]], [[1lzy]] – tuLys + glycoside 
[[1h6m]], [[1at5]], [[1at6]], [[1lzb]], [[1lzc]], [[1lzd]], [[1lze]], [[1lzg]], [[1hew ]]– HEWL + glycoside 
[[1lsy]], [[1lsz]] - HEWL (mutant) + glycoside 
[[1bb6]], [[1bb7]] – RtLys + glycoside 
[[1lmc]] – RtLys + bulgecin 
[[1lmo]], [[1lmp]], [[1lmq]] – RtLys + glucoside 
[[1lsp]] – BsLys + bulgecin 
[[153l]], [[154l]] – Lys +glucoside – goose 

===Phage Lys===

[[2oe4]], [[2oe7]], [[2oe9]], [[2oea]], [[1swz]], [[1cx6]], [[1qtc]], [[1qtd]], [[1qth]], [[1qsb]], [[1qs5]], [[1qs9]], [[1qtb]], [[256l]], [[206l]], [[167l]], [[168l]], [[169l]], [[170l]], [[171l]], [[172l]], [[173l]], [[174l]], [[175l]], [[176l]], [[177l]], [[178l]], [[181l]], [[182l]], [[183l]], [[184l]], [[185l]], [[186l]], [[187l]], [[188l]], [[1nhb]], [[137l]], [[216l]], [[152l]], [[149l]], [[150l]], [[151l]], [[1lyd]], [[2lzm]] - T4Lys – Enterobacteria phage T4 
[[138l]] – T4Lys cross-linked 
[[4lzm]], [[5lzm]], [[6lzm]], [[7lzm]] – T4Lys ionic strength 
[[3l2x]], [[3k2r]], [[3g3v]], [[3g3w]], [[3g3x]], [[2q9d]], [[2q9e]], [[2igc]], [[2ntg]], [[2nth]], [[2ou8]], [[2ou9]], [[1zur]], [[1zwn]], [[1zyt]], [[2cuu]], [[2a4t]] – T4Lys (mutant) spin labeled 
[[3l64]], [[3hwl]], [[3jr6]], [[3gui]], [[3c7w]], [[3c7y]], [[3c7z]], [[3c80]], [[3c81]], [[3c82]], [[3c83]], [[3c8q]], [[3c8r]], [[3c8s]], [[3cdo]], [[3cdq]], [[3cdr]], [[3cdt]], [[3cdv]], [[3f8v]], [[3f9l]], [[3fa0]], [[3fad]], [[3fi5]], [[3dke]], [[3dmv]], [[2o4w]], [[2o79]], [[2o7a]], [[2huk]], [[2hul]], [[2hum]], [[2b7x]], [[2b6t]], [[2b6w]], [[2b6x]], [[2b6y]], [[2b6z]], [[2b70]], [[2b72]], [[2b73]], [[2b74]], [[2b75]], [[1sx7]], [[1swy]], [[1sx2]], [[1t6h]], [[1ssw]], [[1ssy]], [[1t8f]], [[1t8g]], [[1t8a]], [[1t97]], [[1p56]], [[1p5c]], [[1p2l]], [[1p2r]], [[1p36]], [[1p37]], [[1p3n]], [[1p46]], [[1p64]], [[1p6y]], [[1p7s]], [[1pqd]], [[1pqi]], [[1pqj]], [[1pqk]], [[1pqm]], [[1pqo]], [[1oyu]], [[1ks3]], [[1kw5]], [[1kw7]], [[1ky0]], [[1ky1]], [[1l0j]], [[1l0k]], [[1lw9]], [[1lwg]], [[1lwk]], [[1lpy]], [[1llh]], [[1lgu]], [[1li6]], [[1jtm]], [[1jtn]], [[1jqu]], [[1kni]], [[1g06]], [[1g07]], [[1g0g]], [[1g0j]], [[1g0k]], [[1g0l]], [[1g0m]], [[1g0p]], [[1g0q]], [[1g1v]], [[1g1w]], [[1i6s]], [[257l]], [[258l]], [[260l]], [[1epy]], [[1b6i]], [[1cu6]], [[1d9w]], [[1ctw]], [[1cu0]], [[1cu2]], [[1cu3]], [[1cu5]], [[1cv1]], [[1cv4]], [[1cv5]], [[1cv6]], [[1cvk]], [[1cx7]], [[1d2w]], [[1d2y]], [[1d3f]], [[1d3j]], [[1d3m]], [[1d3n]], [[1cv3]], [[1qt3]], [[1qt4]], [[1qt5]], [[1qt6]], [[1qt7]], [[1qt8]], [[1qtv]], [[1qtz]], [[1qud]], [[1qug]], [[1quh]], [[1quo]], [[1qsq]], [[261l]], [[262l]], [[259l]], [[220l]], [[222l]], [[223l]], [[225l]], [[226l]], [[227l]], [[228l]], [[229l]], [[235l]], [[236l]], [[237l]], [[238l]], [[239l]], [[240l]], [[241l]], [[242l]], [[243l]], [[244l]], [[245l]], [[246l]], [[247l]], [[248l]], [[249l]], [[250l]], [[251l]], [[252l]], [[253l]], [[254l]], [[255l]], [[230l]], [[231l]], [[232l]], [[233l]], [[234l]], [[209l]], [[210l]], [[211l]], [[212l]], [[213l]], [[214l]], [[215l]], [[218l]], [[219l]], [[180l]], [[195l]], [[196l]], [[197l]], [[198l]], [[199l]], [[200l]], [[190l]], [[191l]], [[192l]], [[189l]], [[155l]], [[156l]], [[157l]], [[158l]], [[159l]], [[160l]], [[161l]], [[162l]], [[163l]], [[164l]], [[165l]], [[166l]], [[129l]], [[130l]], [[131l]], [[140l]], [[141l]], [[142l]], [[143l]], [[144l]], [[145l]], [[146l]], [[147l]], [[201l]], [[205l]], [[221l]], [[224l]], [[102l]], [[103l]], [[104l]], [[107l]], [[108l]], [[109l]], [[110l]], [[111l]], [[112l]], [[113l]], [[114l]], [[115l]], [[118l]], [[119l]], [[120l]], [[122l]], [[123l]], [[125l]], [[126l]], [[127l]], [[128l]], [[1dya]], [[1dyb]], [[1dyc]], [[1dyd]], [[1dye]], [[1dyf]], [[1dyg]], [[1l00]], [[1l85]], [[1l86]], [[1l87]], [[1l88]], [[1l89]], [[1l90]], [[1l91]], [[1l92]], [[1l93]], [[1l94]], [[1l95]], [[1l96]], [[1l97]], [[1l98]], [[1l99]], [[1lye]], [[1lyf]], [[1lyg]], [[1lyh]], [[1lyi]], [[1lyj]], [[217l]], [[1tla]], [[1l77]], [[1l79]], [[1l80]], [[1l81]], [[1l82]], [[2l78]], [[1l36]], [[1l37]], [[1l38]], [[1l39]], [[1l40]], [[1l41]], [[1l42]], [[1l43]], [[1l44]], [[1l45]], [[1l46]], [[1l47]], [[1l48]], [[1l49]], [[1l50]], [[1l51]], [[1l52]], [[1l53]], [[1l54]], [[1l55]], [[1l56]], [[1l57]], [[1l58]], [[1l59]], [[1l60]], [[1l61]], [[1l62]], [[1l63]], [[1l64]], [[1l65]], [[1l66]], [[1l67]], [[1l68]], [[1l69]], [[1l70]], [[1l71]], [[1l72]], [[1l73]], [[1l74]], [[1l75]], [[1l76]], [[1l17]], [[1l18]], [[1l19]], [[1l20]], [[1l21]], [[1l22]], [[1l23]], [[1l24]], [[1l25]], [[1l26]], [[1l27]], [[1l28]], [[1l29]], [[1l30]], [[1l31]], [[1l32]], [[1l33]], [[1l34]], [[1l35]], [[3lzm]], [[1l01]], [[1l02]], [[1l03]], [[1l04]], [[1l05]], [[1l06]], [[1l07]], [[1l08]], [[1l09]], [[1l10]], [[1l11]], [[1l12]], [[1l13]], [[1l14]], [[1l15]], [[1l16]] – T4Lys (mutant) 
[[1c60]], [[1c61]], [[1c62]], [[1c63]], [[1c64]], [[1c65]], [[1c66]], [[1c67]], [[1c68]], [[1c69]], [[1c6a]], [[1c6b]], [[1c6c]], [[1c6d]], [[1c6e]], [[1c6f]], [[1c6g]], [[1c6h]], [[1c6i]], [[1c6j]], [[1c6k]], [[1c6l]], [[1c6m]], [[1c6n]], [[1c6p]], [[1c6q]], [[1c6t]] - T4Lys (mutant) + noble gas 
[[3ht6]], [[3ht7]], [[3ht8]], [[3ht9]], [[3htb]], [[3hu8]], [[3huq]], [[3guj]], [[3guk]], [[3gul]], [[3gum]], [[3gun]], [[3guo]], [[3gup]], [[3dmx]], [[3dmz]], [[3dn0]], [[3dn1]], [[3dn2]], [[3dn3]], [[3dn4]], [[3dn6]], [[3dn8]], [[3dna]], [[2rb1]], [[2ray]], [[2raz]], [[2rb0]], [[2rb2]], [[2rbn]], [[2rbo]], [[2rbq]], [[2rbr]], [[2rbs]], [[2oty]],[[2otz]], [[1owy]], [[1owz]], [[1ov5]], [[1ov7]], [[1ovh]], [[1ovj]], [[1ovk]], [[1lgw]], [[1lgx]], [[1li2]], [[1li3]], [[1l83]], [[1l84]] – T4Lys (mutant) + benzene derivative 
[[3htd]], [[3htf]], [[3htg]], [[3hu9]], [[3hua]], [[3huk]], [[3hh3]], [[3hh4]], [[3hh5]], [[3hh6]], [[2rbp]], [[2ou0]], [[2f2q]], [[2f32]], [[2f47]], [[1xep]] – T4Lys (mutant) + inhibitor 
[[148l]] - T4Lys (mutant) + glucoside 
[[3d3d]], [[1d9u]] – lamLys + chitohexasaccharide 
[[1am7]] – lamLys - Enterobacteria phage λ 
[[2anv]], [[2anx]] – Lys (mutant)]] - Enterobacteria phage p22 
[[1xjt]], [[1xju]] - Lys - Enterobacteria phage p1 
[[1lba]] - T7Lys - Enterobacteria phage T7 

===Lys protein complex===

[[3m18]], [[3g3a]], [[3g3b]] - HEWL + Variable lymphocyte receptor – Marine lamprey 
[[3a67]], [[3a6b]], [[3a6c]], [[2yss]], [[2eiz]], [[2dqc]], [[2dqd]], [[2dqe]], [[2dqf]], [[2dqg]], [[2dqh]], [[2dqi]], [[2dqj]], [[1j1o]], [[1j1p]], [[1j1x]], [[1ic4]], [[1ic5]], [[1ic7]] – HEWL + mLys antibody HYHEL-10 (mutant) 
[[1xgp]], [[1xgq]], [[1xgr]], [[1xgt]], [[1xgu]] – HEWL + mLys antibody HYHEL-63 
[[3d9a]], [[2eks]], [[1ua6]], [[1c08]], [[3hfm]] – HEWL + mLys antibody HYHEL-10 
[[1uac]] - tuLys C + mLys antibody HYHEL-10 
[[1yqv]], [[2iff]] – HEWL + mLys antibody HYHEL-5 
[[1bql]] – BqLys + mLys antibody HYHEL-5 
[[1ndg]] – HEWL + mLys antibody HYHEL-8 
[[1ndm]] – HEWL + mLys antibody HYHEL-26 
[[1dqj]] - HEWL + mLys antibody HYHEL-63 
[[1nby]], [[1nbz]] – HEWL (mutant) + mLys antibody HYHEL-63 
[[1g7h]], [[1g7i]], [[1g7j]], [[1g7l]], [[1g7m]], [[1kip]], [[1kiq]], [[1kir]] – HEWL + mAnti-HEWL monoclonal antibody (mutant) 
[[1mlc]], [[1vfb]] - HEWL + mIGG1-κ D44.1 FAB 
[[1a2y]] - HEWL (mutant) + mIGG1-κ D1.3 FV 
[[1fdl]] - HEWL + mIGG1-κ D1.3 FAB 
[[1jhl]] – phLys + mIGG1-κ D11.15 FV 
[[1fbi]] – GfLys + mIGG1 F9.13.7 FAB 
[[2znw]], [[2znx]] – HEWL + hSCFV10 antibody 
[[1bvk]] - HEWL + hAnti Lys FV antibody 
[[1dzb]] – tuLys + mSCFV 1F9 
[[1zv5]], [[1zvh]], [[1zvy]], [[1zmy]], [[1ri8]], [[1rjc]], [[1xfp]], [[1jtp]], [[1jtt]], [[1jto]], [[1mel]] - HEWL + cAntibody heavy chain domain – camel 
[[1op9]] - hLys C + cAntibody heavy chain domain 
[[3otp]] – HEWL + EcProtease DO – ''Escherichia coli'' 
[[3f6z]] - HEWL + MLIC – ''Pseudomonas aeruginosa'' 
[[3eba]] – hLys C + hCABHUL6 
[[2qb0]], [[2qar]] – T4Lys/E80 TELSAM domain 
[[2i25]], [[2i26]] - HEWL +NsAntigen receptor PBLA8 variable domain – Nurse shark 
[[1sq2]], [[1t6v]] – HEWL +NsNew Antigen receptor variable domain 
[[1gpq]] – HEWL + EcInhibitor of Vertebrate Lys 
[[1aro]] – T7Lys + T7 RNA polymerase 

===Some Useful External Links===
[http://en.wikipedia.org/wiki/Lysozyme Lysozyme]

[http://en.wikipedia.org/wiki/Glycoside_hydrolase#Retaining_glycoside_hydrolases Retaining Glycoside Hydrolases]

===References===
<references/>

Hen Egg-White (HEW) Lysozyme

2011-03-31T01:11:17Z

Anne Goodling:

<applet load='aln_1H6M_to_1HEW_2.pdb' size='200' frame='true' align='right' caption=' Hen Egg White (HEW) Lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to the active site, PDBid 1HEW' scene='User:Judy_Voet/Lysozyme/Lysozyme1/16' />
Lysozyme was the first enzyme whose X-ray structure was determined <ref> PMID 5840126</ref><ref>Phillips, D. C. The hen egg white lysozyme molecule. Proc. Natl Acad. Sci. USA 57, 483-495 (1967)</ref>. This <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>scene </scene> shows Hen Egg White (HEW) lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to a cleft in the enzyme. David Phillips, who determined the structure in 1965, saw that the cleft was large enough to fit three more saccharide units. He therefore built a model extending the trisaccharide to a
<scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> that fits into the cleft, labeling the sugar subsites A-F<ref> coordinates of the model kindly provided by Louise Johnson</ref>. Alternately click on <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>trisaccharide</scene> and <scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> to turn the modeled portion of the hexasaccharide on and off.
The interesting thing about the model was that the only way that the hexasaccharide would fit into the cleft was if the 4th saccharide (in subsite D) was strained into a <scene name='User:Judy_Voet/Lysozyme/Half-chair/2'>half-chair conformation</scene>. This conformation is what would be necessary for the formation of an oxocarbenium ion (oxionium ion). When the model was studied, <scene name='User:Judy_Voet/Lysozyme/Glu_35/1'>Glu 35</scene> was found to be in an ideal location to act as a general acid catalyst, 3.34 Angstroms from the bridging oxygen between the 4th and 5th saccharide units. <scene name='User:Judy_Voet/Lysozyme/Asp_52/2'>Asp 52</scene> appeared to be too far away (2.69 angstroms) in the static lysozyme structure to have formed a covalent bond with C1 of the half-chair model in the D site, and no covalent intermediate had ever been detected, so Phillips proposed that it acted as an electrostatic stabilizer of the oxonium ion (referred to as The Phillips Mechanism).

Then, in 2001, Stephen Withers published <scene name='User:Judy_Voet/Lysozyme/1h6m/3'>1H6M</scene>,<ref>PMID 11518970</ref> in which Glu 35 had been mutated to Gln to remove the general acid catalyst. The substrate contained NAG-2-fluoro-glucosyl fluoride (NAG2FGlcF). The fluoro group on C-1 does not require acid catalysis to be a good leaving group, and the remaining saccharide, in the absence of the acid necessary to catalyse the second step of the reaction, was demonstrated to form a <scene name='User:Judy_Voet/Lysozyme/Covalent/1'> covalent intermediate</scene>. In this <scene name='User:Judy_Voet/Lysozyme/Superposition/2'>superposition</scene> of the half chair model with 1HEW (greens) and the covalent intermediate in 1H6M (blues), note the relatively small motions of Asp 52 and C1 of the sugar ring in going from the model to the covalent intermediate. to observe the motion from the <scene name='User:Judy_Voet/Lysozyme/Asp52_halfchair/1'>half-chair</scene> to the <scene name='User:Judy_Voet/Lysozyme/Covalent/2'>covalent intermediate</scene> just toggle between the two green links.
<applet load='aln_1H6M_to_1HEW_2.pdb' size='200' frame='true' align='left' caption='NAG-2-deoxy-2-fluoro-glucosyl fluoride (NAG2FGlcF) bound to Glu35Gln HEW Lysozyme PDBid 1H6M' scene='User:Judy_Voet/Lysozyme/1h6m/3'/>

== 3D Structures of Lysozyme ==

===Lys===

[[2x0a]], [[3iju]], [[3ijv]], [[3a8z]], [[2w1y]], [[2w1m]], [[2w1x]], [[2w1l]], [[3e3d]], [[3exd]], [[2zq3]], [[2zq4]], [[3b72]], [[3b6l]], [[2z12]], [[2z18]], [[2z19]], [[2vb1]], [[2hu3]], [[2hub]], [[2htx]], [[2hu1]], [[2yvb]], [[2epe]], [[2g4p]], [[2g4q]], [[2cgi]], [[2b5z]], [[2d4k]], [[2d91]], [[2f2n]], [[2fbb]], [[2c8o]], [[2c8p]], [[2a6u]], [[2aub]], [[2blx]], [[2bly]], [[2a7d]], [[2a7f]], [[1wtm]], [[1wtn]], [[1w6z]], [[1vdp]], [[1vdq]], [[1vds]], [[1vdt]], [[1ved]], [[1v7t]], [[1ps5]], [[2cds]], [[1lj3]], [[1lj4]], [[1lje]], [[1ljf]], [[1ljg]], [[1ljh]], [[1lji]], [[1ljj]], [[1ljk]], [[1jis]], [[1jit]], [[1jiy]], [[1jj0]], [[1jj1]], [[1jj3]], [[1iee]], [[1qio]], [[1f0w]], [[1f10]], [[1dpx]], [[1c10]], [[1qtk]], [[1lz8]], [[1lz9]], [[1bhz]], [[1bgi]], [[1bwh]], [[1bwi]], [[1bwj]], [[1bvx]], [[1hsw]], [[1hsx]], [[1lpi]], [[4lzt]], [[3lzt]], [[1aki]], [[1jpo]], [[1rfp]], [[193l]], [[194l]], [[5lym]], [[1lza]], [[3lyt]], [[4lyt]], [[5lyt]], [[6lyt]], [[2lzt]], [[1lzt]], [[1lzh]], [[2lzh]], [[7lyz]], [[1lyz]], [[2lyz]], [[3lyz]], [[4lyz]], [[5lyz]], [[6lyz]] - HEWL – chicken 
[[1xei]], [[1xej]], [[1xek]], [[1uco]], [[1lma]], [[4lym]] – HEWL low hydration 
[[1lsa]], [[1lsb]], [[1lsc]], [[1lsd]], [[1lse]], [[1lsf]], [[1lys]] – HEWL temperature influence 
[[2lym]], [[3lym]] – HEWL pressure influence 
[[132l]] – HEWL methylated 
[[1rcm]] – HEWL 3 S-S form 
[[2xbr]], [[2xbs]]- HEWL– Raman crystallography 
[[2zwb]], [[1io5]], [[1lzn]] - HEWL– Neutron 
[[1gxv]], [[1gxx]], [[1e8l]] - HEWL- NMR 
[[2hs7]], [[2hso]], [[2hs9]]- HEWL– Powder diffraction 
[[1ir7]], [[1ir8]], [[1ir9]], [[1ioq]], [[1ior]], [[1ios]], [[1iot]], [[1flq]], [[1flu]], [[1flw]], [[1fly]], [[1fn5]], [[1kxw]], [[1kxx]], [[1kxy]], [[1uia]], [[1uib]], [[1uic]], [[1uid]], [[1uie]], [[1uif]], [[1uig]], [[1uih]], [[1lsm]], [[1lsn]], [[1hel]], [[1hem]], [[1hen]], [[1heo]], [[1hep]], [[1heq]], [[1her]] – HEWL (mutant) 
[[1lyo]], [[2lyo]], [[3lyo]], [[4lyo]] – HEWL cross-linked 
[[1xft]] - tuLys – turkey - Powder diffraction 
[[1jse]], [[1tew]], [[135l]], [[2lz2]], [[1lz2]] – tuLys 
[[3lz2]] – tuLys - Laue 
[[3ab6]] – Lys + NAG3 – Hard clam 
[[2x8r]] – Lys GH25 – ''Aspergillus fumigatus'' 
[[3mgw]] – Lys G – Atlantic salmon 
[[3gxk]], [[3gxr]] – Lys G + NAG – Atlantic cod 
[[2fbd]] – HfLys 1 
[[3cb7]] – HfLys 2 
[[2zij]], [[2zik]], [[2zil]], [[2nwd]], [[1iwt]], [[1iwu]], [[1iwv]], [[1iww]], [[1iwx]], [[1iwy]], [[1iwz]], [[1jwr]], [[1jsf]], [[1rex]], [[1lz1]] – hLys – human 
[[1w08]], [[1ix0]], [[1ioc]], [[1ip1]], [[1ip2]], [[1ip3]], [[1ip4]], [[1ip5]], [[1ip6]], [[1ip7]], [[1qsw]], [[1gev]], [[1gez]], [[1gf0]], [[1gf3]], [[1gf4]], [[1gf5]], [[1gf6]], [[1gf7]], [[1i1z]], [[1i20]], [[1i22]], [[1gfr]], [[1gft]], [[1gfu]], [[1gfv]], [[1gf8]], [[1gf9]], [[1gfa]], [[1gfe]], [[1gfg]], [[1gfh]], [[1gfj]], [[1gfk]], [[1inu]], [[1gdx]], [[1ge0]], [[1ge1]], [[1ge2]], [[1ge3]], [[1ge4]], [[1gdw]], [[1gaz]], [[1gb0]], [[1gb2]], [[1gb3]], [[1gb5]], [[1gb6]], [[1gb7]], [[1gb8]], [[1gb9]], [[1gbo]], [[1gbw]], [[1gbx]], [[1gby]], [[1gbz]], [[1gay]], [[1eq4]], [[1eq5]], [[1eqe]], [[1c7p]], [[1di3]], [[1di4]], [[1di5]], [[1c43]], [[1c45]], [[1c46]], [[1ckg]], [[1cj6]], [[1cj7]], [[1cj8]], [[1cj9]], [[1ckc]], [[1ckd]], [[1ckf]], [[1ckh]], [[1b5z]], [[1b70]], [[1b7q]], [[1b7r]], [[1b7s]], [[1b7l]], [[1b7m]], [[1b7n]], [[1b7p]], [[1b5u]], [[1b5v]], [[1b5w]], [[1b5x]], [[1b5y]], [[1bb3]], [[1bb4]], [[2bqa]], [[2bqb]], [[2bqc]], [[2bqd]], [[2bqe]], [[2bqf]], [[2bqg]], [[2bqh]], [[2bqi]], [[2bqj]], [[2bqk]], [[2bql]], [[2bqm]], [[2bqn]], [[2bqo]], [[2mea]], [[2meb]], [[2mec]], [[2med]], [[2mee]], [[2mef]], [[2meg]], [[2meh]], [[2mei]], [[1wqm]], [[1wqn]], [[1wqo]], [[1wqp]], [[1wqq]], [[1wqr]], [[2heb]], [[2hea]], [[2hec]], [[2hed]], [[2hee]], [[2hef]], [[1jka]], [[1jkb]], [[1jkc]], [[1jkd]], [[1loz]], [[1lyy]], [[1oua]], [[1oub]], [[1ouc]], [[1oud]], [[1oue]], [[1ouf]], [[1oug]], [[1ouh]], [[1oui]], [[1ouj]], [[207l]], [[208l ]], [[1yam]], [[1yan]], [[1yao]], [[1yap]], [[1yaq]], [[1lmt]], [[1lhh]], [[1lhi]], [[1lhj]], [[1lhk]], [[1lhl]], [[133l]], [[134l]], [[1lz4]], [[1lz5]], [[1lz6]], [[1laa]], [[1tay]], [[1tby]], [[1tcy]], [[1tdy]], [[2lhm]], [[3lhm]] – hLys (mutant) 
[[1iy3]], [[1iy4]] – hLys - NMR 
[[2z2f]] – Lys – Bovine 
[[2cwi]], [[1el1]], [[1qqy]] – dLys - dog 
[[2z2e]] – dLys (mutant) 
[[1i56]] – dLys – NMR 
[[2dqa]] – Lys – ''Tapes japonica'' 
[[2gv0]] – Lys – Soft-shelled turtle 
[[1ivm]] – mLys M – NMR – mouse 
[[1jfx]] – Lys – ''Streptomyces coelicolor'' 
[[1gd6]] – Lys – ''Bombyx mori'' 
[[1jug]] – Lys – Echidna 
[[1dkj]] – BqLys – Bobwhite quail 
[[2ihl]] – Lys – Japanese quail 
[[1gbs]] – BsLys – Black swan 
[[1lmn]] – RtLys – Rainbow trout 
[[2eql]] – Lys – horse 
[[1ghl]] – phLys – pheasant 
[[1hhl]] – GfLys – Guinea fowl 
[[1lhm]] – Lys (mutant) – yeast 

===Lys small molecules complexes===

[[3fe0]], [[2d4i]], [[2d4j]], [[1v7s]] - HEWL+ D2O 
[[3m3u]] – HEWL Trp fluorescence 
[[2xjw]] - HEWL + CO 
[[1hf4]], [[1lks]] – HEWL + NO3 
[[3a34]], [[3ems]] - HEWL + arginine 
[[2xth]] – cLys + inhibitor K2PtBr6 
[[3a90]], [[3a91]], [[3a92]], [[3a93]], [[3a94]], [[3a95]], [[3a96]], [[3kam]], [[2pc2]], [[2bpu]], [[1t3p]], [[1h87]] – HEWL + rare earth 
[[2d6b]], [[2hg0]], [[1vat]], [[1gwd]], [[1b2k]], [[1lkr]], [[1azf]], [[8lyz]]- HEWL+ halogen 
[[1vat]] - HEWL + Xe 
[[1n4f]] - HEWL + As 
[[2i6z]] - HEWL + Pt drug 
[[2zyp]] - HEWL + poly (allyl amine) 
[[2f30]], [[2f4a]] – HEWL + urea derivative 
[[2f4g]], [[1ykx]], [[1yky]], [[1ykz]], [[1yl0]], [[1yl1]], [[1z55]] - HEWL + alcohol 
[[1dpw]] – HEWL + MPD 
[[1lcn]] – HEWL + SCN 
[[2zxs]] - HEWL with glycine-amide 
[[2h9j]], [[2h9k]], [[1yik]], [[1yil]] - HEWL + cyclam derivative 
[[1b0d]] – HEWL + p-toluene-sulfonate 
[[2q0m]] - HEWL + tricarbonylmanganese 
[[2war]] – HEWL (mutant) + chitopentaose 
[[2h5z]] – HfLys 1 + chitotetraose – House fly 
[[1hnl]] – hLys + glutathione 
[[1dkk]] – BqLys + NO3 

===Lys complex with glucoside===

[[3a3q]] – HEWL (mutant) + NAG 
[[1sf4]], [[1sf6]], [[1sf7]], [[1sfb]], [[1sfg]], [[1ja2]], [[1ja4]], [[1ja6]], [[1ja7]] – HEWL + NAG oligosaccharide – Powder diffraction 
[[1ubz]], [[1d6p]], [[1d6q]], [[1bb5]] – hLys (mutant) + glycoside 
[[1uc0]], [[1re2]], [[1rem]], [[1rey]], [[1rez]], [[1lzr]], [[1lzs]] - hLys + glycoside 
[[1ljn]], [[1jef]], [[1lzy]] – tuLys + glycoside 
[[1h6m]], [[1at5]], [[1at6]], [[1lzb]], [[1lzc]], [[1lzd]], [[1lze]], [[1lzg]], [[1hew ]]– HEWL + glycoside 
[[1lsy]], [[1lsz]] - HEWL (mutant) + glycoside 
[[1bb6]], [[1bb7]] – RtLys + glycoside 
[[1lmc]] – RtLys + bulgecin 
[[1lmo]], [[1lmp]], [[1lmq]] – RtLys + glucoside 
[[1lsp]] – BsLys + bulgecin 
[[153l]], [[154l]] – Lys +glucoside – goose 

===Phage Lys===

[[2oe4]], [[2oe7]], [[2oe9]], [[2oea]], [[1swz]], [[1cx6]], [[1qtc]], [[1qtd]], [[1qth]], [[1qsb]], [[1qs5]], [[1qs9]], [[1qtb]], [[256l]], [[206l]], [[167l]], [[168l]], [[169l]], [[170l]], [[171l]], [[172l]], [[173l]], [[174l]], [[175l]], [[176l]], [[177l]], [[178l]], [[181l]], [[182l]], [[183l]], [[184l]], [[185l]], [[186l]], [[187l]], [[188l]], [[1nhb]], [[137l]], [[216l]], [[152l]], [[149l]], [[150l]], [[151l]], [[1lyd]], [[2lzm]] - T4Lys – Enterobacteria phage T4 
[[138l]] – T4Lys cross-linked 
[[4lzm]], [[5lzm]], [[6lzm]], [[7lzm]] – T4Lys ionic strength 
[[3l2x]], [[3k2r]], [[3g3v]], [[3g3w]], [[3g3x]], [[2q9d]], [[2q9e]], [[2igc]], [[2ntg]], [[2nth]], [[2ou8]], [[2ou9]], [[1zur]], [[1zwn]], [[1zyt]], [[2cuu]], [[2a4t]] – T4Lys (mutant) spin labeled 
[[3l64]], [[3hwl]], [[3jr6]], [[3gui]], [[3c7w]], [[3c7y]], [[3c7z]], [[3c80]], [[3c81]], [[3c82]], [[3c83]], [[3c8q]], [[3c8r]], [[3c8s]], [[3cdo]], [[3cdq]], [[3cdr]], [[3cdt]], [[3cdv]], [[3f8v]], [[3f9l]], [[3fa0]], [[3fad]], [[3fi5]], [[3dke]], [[3dmv]], [[2o4w]], [[2o79]], [[2o7a]], [[2huk]], [[2hul]], [[2hum]], [[2b7x]], [[2b6t]], [[2b6w]], [[2b6x]], [[2b6y]], [[2b6z]], [[2b70]], [[2b72]], [[2b73]], [[2b74]], [[2b75]], [[1sx7]], [[1swy]], [[1sx2]], [[1t6h]], [[1ssw]], [[1ssy]], [[1t8f]], [[1t8g]], [[1t8a]], [[1t97]], [[1p56]], [[1p5c]], [[1p2l]], [[1p2r]], [[1p36]], [[1p37]], [[1p3n]], [[1p46]], [[1p64]], [[1p6y]], [[1p7s]], [[1pqd]], [[1pqi]], [[1pqj]], [[1pqk]], [[1pqm]], [[1pqo]], [[1oyu]], [[1ks3]], [[1kw5]], [[1kw7]], [[1ky0]], [[1ky1]], [[1l0j]], [[1l0k]], [[1lw9]], [[1lwg]], [[1lwk]], [[1lpy]], [[1llh]], [[1lgu]], [[1li6]], [[1jtm]], [[1jtn]], [[1jqu]], [[1kni]], [[1g06]], [[1g07]], [[1g0g]], [[1g0j]], [[1g0k]], [[1g0l]], [[1g0m]], [[1g0p]], [[1g0q]], [[1g1v]], [[1g1w]], [[1i6s]], [[257l]], [[258l]], [[260l]], [[1epy]], [[1b6i]], [[1cu6]], [[1d9w]], [[1ctw]], [[1cu0]], [[1cu2]], [[1cu3]], [[1cu5]], [[1cv1]], [[1cv4]], [[1cv5]], [[1cv6]], [[1cvk]], [[1cx7]], [[1d2w]], [[1d2y]], [[1d3f]], [[1d3j]], [[1d3m]], [[1d3n]], [[1cv3]], [[1qt3]], [[1qt4]], [[1qt5]], [[1qt6]], [[1qt7]], [[1qt8]], [[1qtv]], [[1qtz]], [[1qud]], [[1qug]], [[1quh]], [[1quo]], [[1qsq]], [[261l]], [[262l]], [[259l]], [[220l]], [[222l]], [[223l]], [[225l]], [[226l]], [[227l]], [[228l]], [[229l]], [[235l]], [[236l]], [[237l]], [[238l]], [[239l]], [[240l]], [[241l]], [[242l]], [[243l]], [[244l]], [[245l]], [[246l]], [[247l]], [[248l]], [[249l]], [[250l]], [[251l]], [[252l]], [[253l]], [[254l]], [[255l]], [[230l]], [[231l]], [[232l]], [[233l]], [[234l]], [[209l]], [[210l]], [[211l]], [[212l]], [[213l]], [[214l]], [[215l]], [[218l]], [[219l]], [[180l]], [[195l]], [[196l]], [[197l]], [[198l]], [[199l]], [[200l]], [[190l]], [[191l]], [[192l]], [[189l]], [[155l]], [[156l]], [[157l]], [[158l]], [[159l]], [[160l]], [[161l]], [[162l]], [[163l]], [[164l]], [[165l]], [[166l]], [[129l]], [[130l]], [[131l]], [[140l]], [[141l]], [[142l]], [[143l]], [[144l]], [[145l]], [[146l]], [[147l]], [[201l]], [[205l]], [[221l]], [[224l]], [[102l]], [[103l]], [[104l]], [[107l]], [[108l]], [[109l]], [[110l]], [[111l]], [[112l]], [[113l]], [[114l]], [[115l]], [[118l]], [[119l]], [[120l]], [[122l]], [[123l]], [[125l]], [[126l]], [[127l]], [[128l]], [[1dya]], [[1dyb]], [[1dyc]], [[1dyd]], [[1dye]], [[1dyf]], [[1dyg]], [[1l00]], [[1l85]], [[1l86]], [[1l87]], [[1l88]], [[1l89]], [[1l90]], [[1l91]], [[1l92]], [[1l93]], [[1l94]], [[1l95]], [[1l96]], [[1l97]], [[1l98]], [[1l99]], [[1lye]], [[1lyf]], [[1lyg]], [[1lyh]], [[1lyi]], [[1lyj]], [[217l]], [[1tla]], [[1l77]], [[1l79]], [[1l80]], [[1l81]], [[1l82]], [[2l78]], [[1l36]], [[1l37]], [[1l38]], [[1l39]], [[1l40]], [[1l41]], [[1l42]], [[1l43]], [[1l44]], [[1l45]], [[1l46]], [[1l47]], [[1l48]], [[1l49]], [[1l50]], [[1l51]], [[1l52]], [[1l53]], [[1l54]], [[1l55]], [[1l56]], [[1l57]], [[1l58]], [[1l59]], [[1l60]], [[1l61]], [[1l62]], [[1l63]], [[1l64]], [[1l65]], [[1l66]], [[1l67]], [[1l68]], [[1l69]], [[1l70]], [[1l71]], [[1l72]], [[1l73]], [[1l74]], [[1l75]], [[1l76]], [[1l17]], [[1l18]], [[1l19]], [[1l20]], [[1l21]], [[1l22]], [[1l23]], [[1l24]], [[1l25]], [[1l26]], [[1l27]], [[1l28]], [[1l29]], [[1l30]], [[1l31]], [[1l32]], [[1l33]], [[1l34]], [[1l35]], [[3lzm]], [[1l01]], [[1l02]], [[1l03]], [[1l04]], [[1l05]], [[1l06]], [[1l07]], [[1l08]], [[1l09]], [[1l10]], [[1l11]], [[1l12]], [[1l13]], [[1l14]], [[1l15]], [[1l16]] – T4Lys (mutant) 
[[1c60]], [[1c61]], [[1c62]], [[1c63]], [[1c64]], [[1c65]], [[1c66]], [[1c67]], [[1c68]], [[1c69]], [[1c6a]], [[1c6b]], [[1c6c]], [[1c6d]], [[1c6e]], [[1c6f]], [[1c6g]], [[1c6h]], [[1c6i]], [[1c6j]], [[1c6k]], [[1c6l]], [[1c6m]], [[1c6n]], [[1c6p]], [[1c6q]], [[1c6t]] - T4Lys (mutant) + noble gas 
[[3ht6]], [[3ht7]], [[3ht8]], [[3ht9]], [[3htb]], [[3hu8]], [[3huq]], [[3guj]], [[3guk]], [[3gul]], [[3gum]], [[3gun]], [[3guo]], [[3gup]], [[3dmx]], [[3dmz]], [[3dn0]], [[3dn1]], [[3dn2]], [[3dn3]], [[3dn4]], [[3dn6]], [[3dn8]], [[3dna]], [[2rb1]], [[2ray]], [[2raz]], [[2rb0]], [[2rb2]], [[2rbn]], [[2rbo]], [[2rbq]], [[2rbr]], [[2rbs]], [[2oty]],[[2otz]], [[1owy]], [[1owz]], [[1ov5]], [[1ov7]], [[1ovh]], [[1ovj]], [[1ovk]], [[1lgw]], [[1lgx]], [[1li2]], [[1li3]], [[1l83]], [[1l84]] – T4Lys (mutant) + benzene derivative 
[[3htd]], [[3htf]], [[3htg]], [[3hu9]], [[3hua]], [[3huk]], [[3hh3]], [[3hh4]], [[3hh5]], [[3hh6]], [[2rbp]], [[2ou0]], [[2f2q]], [[2f32]], [[2f47]], [[1xep]] – T4Lys (mutant) + inhibitor 
[[148l]] - T4Lys (mutant) + glucoside 
[[3d3d]], [[1d9u]] – lamLys + chitohexasaccharide 
[[1am7]] – lamLys - Enterobacteria phage λ 
[[2anv]], [[2anx]] – Lys (mutant)]] - Enterobacteria phage p22 
[[1xjt]], [[1xju]] - Lys - Enterobacteria phage p1 
[[1lba]] - T7Lys - Enterobacteria phage T7 

===Lys protein complex===

[[3m18]], [[3g3a]], [[3g3b]] - HEWL + Variable lymphocyte receptor – Marine lamprey 
[[3a67]], [[3a6b]], [[3a6c]], [[2yss]], [[2eiz]], [[2dqc]], [[2dqd]], [[2dqe]], [[2dqf]], [[2dqg]], [[2dqh]], [[2dqi]], [[2dqj]], [[1j1o]], [[1j1p]], [[1j1x]], [[1ic4]], [[1ic5]], [[1ic7]] – HEWL + mLys antibody HYHEL-10 (mutant) 
[[1xgp]], [[1xgq]], [[1xgr]], [[1xgt]], [[1xgu]] – HEWL + mLys antibody HYHEL-63 
[[3d9a]], [[2eks]], [[1ua6]], [[1c08]], [[3hfm]] – HEWL + mLys antibody HYHEL-10 
[[1uac]] - tuLys C + mLys antibody HYHEL-10 
[[1yqv]], [[2iff]] – HEWL + mLys antibody HYHEL-5 
[[1bql]] – BqLys + mLys antibody HYHEL-5 
[[1ndg]] – HEWL + mLys antibody HYHEL-8 
[[1ndm]] – HEWL + mLys antibody HYHEL-26 
[[1dqj]] - HEWL + mLys antibody HYHEL-63 
[[1nby]], [[1nbz]] – HEWL (mutant) + mLys antibody HYHEL-63 
[[1g7h]], [[1g7i]], [[1g7j]], [[1g7l]], [[1g7m]], [[1kip]], [[1kiq]], [[1kir]] – HEWL + mAnti-HEWL monoclonal antibody (mutant) 
[[1mlc]], [[1vfb]] - HEWL + mIGG1-κ D44.1 FAB 
[[1a2y]] - HEWL (mutant) + mIGG1-κ D1.3 FV 
[[1fdl]] - HEWL + mIGG1-κ D1.3 FAB 
[[1jhl]] – phLys + mIGG1-κ D11.15 FV 
[[1fbi]] – GfLys + mIGG1 F9.13.7 FAB 
[[2znw]], [[2znx]] – HEWL + hSCFV10 antibody 
[[1bvk]] - HEWL + hAnti Lys FV antibody 
[[1dzb]] – tuLys + mSCFV 1F9 
[[1zv5]], [[1zvh]], [[1zvy]], [[1zmy]], [[1ri8]], [[1rjc]], [[1xfp]], [[1jtp]], [[1jtt]], [[1jto]], [[1mel]] - HEWL + cAntibody heavy chain domain – camel 
[[1op9]] - hLys C + cAntibody heavy chain domain 
[[3otp]] – HEWL + EcProtease DO – ''Escherichia coli'' 
[[3f6z]] - HEWL + MLIC – ''Pseudomonas aeruginosa'' 
[[3eba]] – hLys C + hCABHUL6 
[[2qb0]], [[2qar]] – T4Lys/E80 TELSAM domain 
[[2i25]], [[2i26]] - HEWL +NsAntigen receptor PBLA8 variable domain – Nurse shark 
[[1sq2]], [[1t6v]] – HEWL +NsNew Antigen receptor variable domain 
[[1gpq]] – HEWL + EcInhibitor of Vertebrate Lys 
[[1aro]] – T7Lys + T7 RNA polymerase 

===Some Useful External Links===
[http://en.wikipedia.org/wiki/Lysozyme Lysozyme]

[http://en.wikipedia.org/wiki/Glycoside_hydrolase#Retaining_glycoside_hydrolases Retaining Glycoside Hydrolases]

===References===
<references/>

Hen Egg-White (HEW) Lysozyme

2011-03-31T01:09:25Z

Anne Goodling:

<applet load='aln_1H6M_to_1HEW_2.pdb' size='200' frame='true' align='right' caption=' Hen Egg White (HEW) Lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to the active site, PDBid 1HEW' scene='User:Judy_Voet/Lysozyme/Lysozyme1/16' />
Lysozyme was the first enzyme whose X-ray structure was determined <ref> PMID 5840126</ref><ref>Phillips, D. C. The hen egg white lysozyme molecule. Proc. Natl Acad. Sci. USA 57, 483-495 (1967)</ref>. This <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>scene </scene> shows Hen Egg White (HEW) lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to a cleft in the enzyme. David Phillips, who determined the structure in 1965, saw that the cleft was large enough to fit three more saccharide units. He therefore built a model extending the trisaccharide to a
<scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> that fits into the cleft, labeling the sugar subsites A-F<ref> coordinates of the model kindly provided by Louise Johnson</ref>. Alternately click on <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>trisaccharide</scene> and <scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> to turn the modeled portion of the hexasaccharide on and off.
The interesting thing about the model was that the only way that the hexasaccharide would fit into the cleft was if the 4th saccharide (in subsite D) was strained into a <scene name='User:Judy_Voet/Lysozyme/Half-chair/2'>half-chair conformation</scene>. This conformation is what would be necessary for the formation of an oxocarbenium ion (oxionium ion). When the model was studied, <scene name='User:Judy_Voet/Lysozyme/Glu_35/1'>Glu 35</scene> was found to be in an ideal location to act as a general acid catalyst, 3.34 Angstroms from the bridging oxygen between the 4th and 5th saccharide units. <scene name='User:Judy_Voet/Lysozyme/Asp_52/2'>Asp 52</scene> appeared to be too far away (2.69 angstroms) in the static lysozyme structure to have formed a covalent bond with C1 of the half-chair model in the D site, and no covalent intermediate had ever been detected, so Phillips proposed that it acted as an electrostatic stabilizer of the oxonium ion (referred to as The Phillips Mechanism).

Then, in 2001, Stephen Withers published <scene name='User:Judy_Voet/Lysozyme/1h6m/3'>1H6M</scene>,<ref>PMID 11518970</ref> in which Glu 35 had been mutated to Gln to remove the general acid catalyst. The substrate contained NAG-2-fluoro-glucosyl fluoride (NAG2FGlcF). The fluoro group on C-1 does not require acid catalysis to be a good leaving group, and the remaining saccharide, in the absence of the acid necessary to catalyse the second step of the reaction, was demonstrated to form a <scene name='User:Judy_Voet/Lysozyme/Covalent/1'> covalent intermediate</scene>. In this <scene name='User:Judy_Voet/Lysozyme/Superposition/2'>superposition</scene> of the half chair model with 1HEW (greens) and the covalent intermediate in 1H6M (blues), note the relatively small motions of Asp 52 and C1 of the sugar ring in going from the model to the covalent intermediate. to observe the motion from the <scene name='User:Judy_Voet/Lysozyme/Asp52_halfchair/1'>half-chair</scene> to the <scene name='User:Judy_Voet/Lysozyme/Covalent/2'>covalent intermediate</scene> just toggle between the two green links.

<applet load='aln_1H6M_to_1HEW_2.pdb' size='200' frame='true' align='right' caption='NAG-2-deoxy-2-fluoro-glucosyl fluoride (NAG2FGlcF) bound to Glu35Gln HEW Lysozyme PDBid 1H6M' scene='User:Judy_Voet/Lysozyme/1h6m/3'/>

== 3D Structures of Lysozyme ==

===Lys===

[[2x0a]], [[3iju]], [[3ijv]], [[3a8z]], [[2w1y]], [[2w1m]], [[2w1x]], [[2w1l]], [[3e3d]], [[3exd]], [[2zq3]], [[2zq4]], [[3b72]], [[3b6l]], [[2z12]], [[2z18]], [[2z19]], [[2vb1]], [[2hu3]], [[2hub]], [[2htx]], [[2hu1]], [[2yvb]], [[2epe]], [[2g4p]], [[2g4q]], [[2cgi]], [[2b5z]], [[2d4k]], [[2d91]], [[2f2n]], [[2fbb]], [[2c8o]], [[2c8p]], [[2a6u]], [[2aub]], [[2blx]], [[2bly]], [[2a7d]], [[2a7f]], [[1wtm]], [[1wtn]], [[1w6z]], [[1vdp]], [[1vdq]], [[1vds]], [[1vdt]], [[1ved]], [[1v7t]], [[1ps5]], [[2cds]], [[1lj3]], [[1lj4]], [[1lje]], [[1ljf]], [[1ljg]], [[1ljh]], [[1lji]], [[1ljj]], [[1ljk]], [[1jis]], [[1jit]], [[1jiy]], [[1jj0]], [[1jj1]], [[1jj3]], [[1iee]], [[1qio]], [[1f0w]], [[1f10]], [[1dpx]], [[1c10]], [[1qtk]], [[1lz8]], [[1lz9]], [[1bhz]], [[1bgi]], [[1bwh]], [[1bwi]], [[1bwj]], [[1bvx]], [[1hsw]], [[1hsx]], [[1lpi]], [[4lzt]], [[3lzt]], [[1aki]], [[1jpo]], [[1rfp]], [[193l]], [[194l]], [[5lym]], [[1lza]], [[3lyt]], [[4lyt]], [[5lyt]], [[6lyt]], [[2lzt]], [[1lzt]], [[1lzh]], [[2lzh]], [[7lyz]], [[1lyz]], [[2lyz]], [[3lyz]], [[4lyz]], [[5lyz]], [[6lyz]] - HEWL – chicken 
[[1xei]], [[1xej]], [[1xek]], [[1uco]], [[1lma]], [[4lym]] – HEWL low hydration 
[[1lsa]], [[1lsb]], [[1lsc]], [[1lsd]], [[1lse]], [[1lsf]], [[1lys]] – HEWL temperature influence 
[[2lym]], [[3lym]] – HEWL pressure influence 
[[132l]] – HEWL methylated 
[[1rcm]] – HEWL 3 S-S form 
[[2xbr]], [[2xbs]]- HEWL– Raman crystallography 
[[2zwb]], [[1io5]], [[1lzn]] - HEWL– Neutron 
[[1gxv]], [[1gxx]], [[1e8l]] - HEWL- NMR 
[[2hs7]], [[2hso]], [[2hs9]]- HEWL– Powder diffraction 
[[1ir7]], [[1ir8]], [[1ir9]], [[1ioq]], [[1ior]], [[1ios]], [[1iot]], [[1flq]], [[1flu]], [[1flw]], [[1fly]], [[1fn5]], [[1kxw]], [[1kxx]], [[1kxy]], [[1uia]], [[1uib]], [[1uic]], [[1uid]], [[1uie]], [[1uif]], [[1uig]], [[1uih]], [[1lsm]], [[1lsn]], [[1hel]], [[1hem]], [[1hen]], [[1heo]], [[1hep]], [[1heq]], [[1her]] – HEWL (mutant) 
[[1lyo]], [[2lyo]], [[3lyo]], [[4lyo]] – HEWL cross-linked 
[[1xft]] - tuLys – turkey - Powder diffraction 
[[1jse]], [[1tew]], [[135l]], [[2lz2]], [[1lz2]] – tuLys 
[[3lz2]] – tuLys - Laue 
[[3ab6]] – Lys + NAG3 – Hard clam 
[[2x8r]] – Lys GH25 – ''Aspergillus fumigatus'' 
[[3mgw]] – Lys G – Atlantic salmon 
[[3gxk]], [[3gxr]] – Lys G + NAG – Atlantic cod 
[[2fbd]] – HfLys 1 
[[3cb7]] – HfLys 2 
[[2zij]], [[2zik]], [[2zil]], [[2nwd]], [[1iwt]], [[1iwu]], [[1iwv]], [[1iww]], [[1iwx]], [[1iwy]], [[1iwz]], [[1jwr]], [[1jsf]], [[1rex]], [[1lz1]] – hLys – human 
[[1w08]], [[1ix0]], [[1ioc]], [[1ip1]], [[1ip2]], [[1ip3]], [[1ip4]], [[1ip5]], [[1ip6]], [[1ip7]], [[1qsw]], [[1gev]], [[1gez]], [[1gf0]], [[1gf3]], [[1gf4]], [[1gf5]], [[1gf6]], [[1gf7]], [[1i1z]], [[1i20]], [[1i22]], [[1gfr]], [[1gft]], [[1gfu]], [[1gfv]], [[1gf8]], [[1gf9]], [[1gfa]], [[1gfe]], [[1gfg]], [[1gfh]], [[1gfj]], [[1gfk]], [[1inu]], [[1gdx]], [[1ge0]], [[1ge1]], [[1ge2]], [[1ge3]], [[1ge4]], [[1gdw]], [[1gaz]], [[1gb0]], [[1gb2]], [[1gb3]], [[1gb5]], [[1gb6]], [[1gb7]], [[1gb8]], [[1gb9]], [[1gbo]], [[1gbw]], [[1gbx]], [[1gby]], [[1gbz]], [[1gay]], [[1eq4]], [[1eq5]], [[1eqe]], [[1c7p]], [[1di3]], [[1di4]], [[1di5]], [[1c43]], [[1c45]], [[1c46]], [[1ckg]], [[1cj6]], [[1cj7]], [[1cj8]], [[1cj9]], [[1ckc]], [[1ckd]], [[1ckf]], [[1ckh]], [[1b5z]], [[1b70]], [[1b7q]], [[1b7r]], [[1b7s]], [[1b7l]], [[1b7m]], [[1b7n]], [[1b7p]], [[1b5u]], [[1b5v]], [[1b5w]], [[1b5x]], [[1b5y]], [[1bb3]], [[1bb4]], [[2bqa]], [[2bqb]], [[2bqc]], [[2bqd]], [[2bqe]], [[2bqf]], [[2bqg]], [[2bqh]], [[2bqi]], [[2bqj]], [[2bqk]], [[2bql]], [[2bqm]], [[2bqn]], [[2bqo]], [[2mea]], [[2meb]], [[2mec]], [[2med]], [[2mee]], [[2mef]], [[2meg]], [[2meh]], [[2mei]], [[1wqm]], [[1wqn]], [[1wqo]], [[1wqp]], [[1wqq]], [[1wqr]], [[2heb]], [[2hea]], [[2hec]], [[2hed]], [[2hee]], [[2hef]], [[1jka]], [[1jkb]], [[1jkc]], [[1jkd]], [[1loz]], [[1lyy]], [[1oua]], [[1oub]], [[1ouc]], [[1oud]], [[1oue]], [[1ouf]], [[1oug]], [[1ouh]], [[1oui]], [[1ouj]], [[207l]], [[208l ]], [[1yam]], [[1yan]], [[1yao]], [[1yap]], [[1yaq]], [[1lmt]], [[1lhh]], [[1lhi]], [[1lhj]], [[1lhk]], [[1lhl]], [[133l]], [[134l]], [[1lz4]], [[1lz5]], [[1lz6]], [[1laa]], [[1tay]], [[1tby]], [[1tcy]], [[1tdy]], [[2lhm]], [[3lhm]] – hLys (mutant) 
[[1iy3]], [[1iy4]] – hLys - NMR 
[[2z2f]] – Lys – Bovine 
[[2cwi]], [[1el1]], [[1qqy]] – dLys - dog 
[[2z2e]] – dLys (mutant) 
[[1i56]] – dLys – NMR 
[[2dqa]] – Lys – ''Tapes japonica'' 
[[2gv0]] – Lys – Soft-shelled turtle 
[[1ivm]] – mLys M – NMR – mouse 
[[1jfx]] – Lys – ''Streptomyces coelicolor'' 
[[1gd6]] – Lys – ''Bombyx mori'' 
[[1jug]] – Lys – Echidna 
[[1dkj]] – BqLys – Bobwhite quail 
[[2ihl]] – Lys – Japanese quail 
[[1gbs]] – BsLys – Black swan 
[[1lmn]] – RtLys – Rainbow trout 
[[2eql]] – Lys – horse 
[[1ghl]] – phLys – pheasant 
[[1hhl]] – GfLys – Guinea fowl 
[[1lhm]] – Lys (mutant) – yeast 

===Lys small molecules complexes===

[[3fe0]], [[2d4i]], [[2d4j]], [[1v7s]] - HEWL+ D2O 
[[3m3u]] – HEWL Trp fluorescence 
[[2xjw]] - HEWL + CO 
[[1hf4]], [[1lks]] – HEWL + NO3 
[[3a34]], [[3ems]] - HEWL + arginine 
[[2xth]] – cLys + inhibitor K2PtBr6 
[[3a90]], [[3a91]], [[3a92]], [[3a93]], [[3a94]], [[3a95]], [[3a96]], [[3kam]], [[2pc2]], [[2bpu]], [[1t3p]], [[1h87]] – HEWL + rare earth 
[[2d6b]], [[2hg0]], [[1vat]], [[1gwd]], [[1b2k]], [[1lkr]], [[1azf]], [[8lyz]]- HEWL+ halogen 
[[1vat]] - HEWL + Xe 
[[1n4f]] - HEWL + As 
[[2i6z]] - HEWL + Pt drug 
[[2zyp]] - HEWL + poly (allyl amine) 
[[2f30]], [[2f4a]] – HEWL + urea derivative 
[[2f4g]], [[1ykx]], [[1yky]], [[1ykz]], [[1yl0]], [[1yl1]], [[1z55]] - HEWL + alcohol 
[[1dpw]] – HEWL + MPD 
[[1lcn]] – HEWL + SCN 
[[2zxs]] - HEWL with glycine-amide 
[[2h9j]], [[2h9k]], [[1yik]], [[1yil]] - HEWL + cyclam derivative 
[[1b0d]] – HEWL + p-toluene-sulfonate 
[[2q0m]] - HEWL + tricarbonylmanganese 
[[2war]] – HEWL (mutant) + chitopentaose 
[[2h5z]] – HfLys 1 + chitotetraose – House fly 
[[1hnl]] – hLys + glutathione 
[[1dkk]] – BqLys + NO3 

===Lys complex with glucoside===

[[3a3q]] – HEWL (mutant) + NAG 
[[1sf4]], [[1sf6]], [[1sf7]], [[1sfb]], [[1sfg]], [[1ja2]], [[1ja4]], [[1ja6]], [[1ja7]] – HEWL + NAG oligosaccharide – Powder diffraction 
[[1ubz]], [[1d6p]], [[1d6q]], [[1bb5]] – hLys (mutant) + glycoside 
[[1uc0]], [[1re2]], [[1rem]], [[1rey]], [[1rez]], [[1lzr]], [[1lzs]] - hLys + glycoside 
[[1ljn]], [[1jef]], [[1lzy]] – tuLys + glycoside 
[[1h6m]], [[1at5]], [[1at6]], [[1lzb]], [[1lzc]], [[1lzd]], [[1lze]], [[1lzg]], [[1hew ]]– HEWL + glycoside 
[[1lsy]], [[1lsz]] - HEWL (mutant) + glycoside 
[[1bb6]], [[1bb7]] – RtLys + glycoside 
[[1lmc]] – RtLys + bulgecin 
[[1lmo]], [[1lmp]], [[1lmq]] – RtLys + glucoside 
[[1lsp]] – BsLys + bulgecin 
[[153l]], [[154l]] – Lys +glucoside – goose 

===Phage Lys===

[[2oe4]], [[2oe7]], [[2oe9]], [[2oea]], [[1swz]], [[1cx6]], [[1qtc]], [[1qtd]], [[1qth]], [[1qsb]], [[1qs5]], [[1qs9]], [[1qtb]], [[256l]], [[206l]], [[167l]], [[168l]], [[169l]], [[170l]], [[171l]], [[172l]], [[173l]], [[174l]], [[175l]], [[176l]], [[177l]], [[178l]], [[181l]], [[182l]], [[183l]], [[184l]], [[185l]], [[186l]], [[187l]], [[188l]], [[1nhb]], [[137l]], [[216l]], [[152l]], [[149l]], [[150l]], [[151l]], [[1lyd]], [[2lzm]] - T4Lys – Enterobacteria phage T4 
[[138l]] – T4Lys cross-linked 
[[4lzm]], [[5lzm]], [[6lzm]], [[7lzm]] – T4Lys ionic strength 
[[3l2x]], [[3k2r]], [[3g3v]], [[3g3w]], [[3g3x]], [[2q9d]], [[2q9e]], [[2igc]], [[2ntg]], [[2nth]], [[2ou8]], [[2ou9]], [[1zur]], [[1zwn]], [[1zyt]], [[2cuu]], [[2a4t]] – T4Lys (mutant) spin labeled 
[[3l64]], [[3hwl]], [[3jr6]], [[3gui]], [[3c7w]], [[3c7y]], [[3c7z]], [[3c80]], [[3c81]], [[3c82]], [[3c83]], [[3c8q]], [[3c8r]], [[3c8s]], [[3cdo]], [[3cdq]], [[3cdr]], [[3cdt]], [[3cdv]], [[3f8v]], [[3f9l]], [[3fa0]], [[3fad]], [[3fi5]], [[3dke]], [[3dmv]], [[2o4w]], [[2o79]], [[2o7a]], [[2huk]], [[2hul]], [[2hum]], [[2b7x]], [[2b6t]], [[2b6w]], [[2b6x]], [[2b6y]], [[2b6z]], [[2b70]], [[2b72]], [[2b73]], [[2b74]], [[2b75]], [[1sx7]], [[1swy]], [[1sx2]], [[1t6h]], [[1ssw]], [[1ssy]], [[1t8f]], [[1t8g]], [[1t8a]], [[1t97]], [[1p56]], [[1p5c]], [[1p2l]], [[1p2r]], [[1p36]], [[1p37]], [[1p3n]], [[1p46]], [[1p64]], [[1p6y]], [[1p7s]], [[1pqd]], [[1pqi]], [[1pqj]], [[1pqk]], [[1pqm]], [[1pqo]], [[1oyu]], [[1ks3]], [[1kw5]], [[1kw7]], [[1ky0]], [[1ky1]], [[1l0j]], [[1l0k]], [[1lw9]], [[1lwg]], [[1lwk]], [[1lpy]], [[1llh]], [[1lgu]], [[1li6]], [[1jtm]], [[1jtn]], [[1jqu]], [[1kni]], [[1g06]], [[1g07]], [[1g0g]], [[1g0j]], [[1g0k]], [[1g0l]], [[1g0m]], [[1g0p]], [[1g0q]], [[1g1v]], [[1g1w]], [[1i6s]], [[257l]], [[258l]], [[260l]], [[1epy]], [[1b6i]], [[1cu6]], [[1d9w]], [[1ctw]], [[1cu0]], [[1cu2]], [[1cu3]], [[1cu5]], [[1cv1]], [[1cv4]], [[1cv5]], [[1cv6]], [[1cvk]], [[1cx7]], [[1d2w]], [[1d2y]], [[1d3f]], [[1d3j]], [[1d3m]], [[1d3n]], [[1cv3]], [[1qt3]], [[1qt4]], [[1qt5]], [[1qt6]], [[1qt7]], [[1qt8]], [[1qtv]], [[1qtz]], [[1qud]], [[1qug]], [[1quh]], [[1quo]], [[1qsq]], [[261l]], [[262l]], [[259l]], [[220l]], [[222l]], [[223l]], [[225l]], [[226l]], [[227l]], [[228l]], [[229l]], [[235l]], [[236l]], [[237l]], [[238l]], [[239l]], [[240l]], [[241l]], [[242l]], [[243l]], [[244l]], [[245l]], [[246l]], [[247l]], [[248l]], [[249l]], [[250l]], [[251l]], [[252l]], [[253l]], [[254l]], [[255l]], [[230l]], [[231l]], [[232l]], [[233l]], [[234l]], [[209l]], [[210l]], [[211l]], [[212l]], [[213l]], [[214l]], [[215l]], [[218l]], [[219l]], [[180l]], [[195l]], [[196l]], [[197l]], [[198l]], [[199l]], [[200l]], [[190l]], [[191l]], [[192l]], [[189l]], [[155l]], [[156l]], [[157l]], [[158l]], [[159l]], [[160l]], [[161l]], [[162l]], [[163l]], [[164l]], [[165l]], [[166l]], [[129l]], [[130l]], [[131l]], [[140l]], [[141l]], [[142l]], [[143l]], [[144l]], [[145l]], [[146l]], [[147l]], [[201l]], [[205l]], [[221l]], [[224l]], [[102l]], [[103l]], [[104l]], [[107l]], [[108l]], [[109l]], [[110l]], [[111l]], [[112l]], [[113l]], [[114l]], [[115l]], [[118l]], [[119l]], [[120l]], [[122l]], [[123l]], [[125l]], [[126l]], [[127l]], [[128l]], [[1dya]], [[1dyb]], [[1dyc]], [[1dyd]], [[1dye]], [[1dyf]], [[1dyg]], [[1l00]], [[1l85]], [[1l86]], [[1l87]], [[1l88]], [[1l89]], [[1l90]], [[1l91]], [[1l92]], [[1l93]], [[1l94]], [[1l95]], [[1l96]], [[1l97]], [[1l98]], [[1l99]], [[1lye]], [[1lyf]], [[1lyg]], [[1lyh]], [[1lyi]], [[1lyj]], [[217l]], [[1tla]], [[1l77]], [[1l79]], [[1l80]], [[1l81]], [[1l82]], [[2l78]], [[1l36]], [[1l37]], [[1l38]], [[1l39]], [[1l40]], [[1l41]], [[1l42]], [[1l43]], [[1l44]], [[1l45]], [[1l46]], [[1l47]], [[1l48]], [[1l49]], [[1l50]], [[1l51]], [[1l52]], [[1l53]], [[1l54]], [[1l55]], [[1l56]], [[1l57]], [[1l58]], [[1l59]], [[1l60]], [[1l61]], [[1l62]], [[1l63]], [[1l64]], [[1l65]], [[1l66]], [[1l67]], [[1l68]], [[1l69]], [[1l70]], [[1l71]], [[1l72]], [[1l73]], [[1l74]], [[1l75]], [[1l76]], [[1l17]], [[1l18]], [[1l19]], [[1l20]], [[1l21]], [[1l22]], [[1l23]], [[1l24]], [[1l25]], [[1l26]], [[1l27]], [[1l28]], [[1l29]], [[1l30]], [[1l31]], [[1l32]], [[1l33]], [[1l34]], [[1l35]], [[3lzm]], [[1l01]], [[1l02]], [[1l03]], [[1l04]], [[1l05]], [[1l06]], [[1l07]], [[1l08]], [[1l09]], [[1l10]], [[1l11]], [[1l12]], [[1l13]], [[1l14]], [[1l15]], [[1l16]] – T4Lys (mutant) 
[[1c60]], [[1c61]], [[1c62]], [[1c63]], [[1c64]], [[1c65]], [[1c66]], [[1c67]], [[1c68]], [[1c69]], [[1c6a]], [[1c6b]], [[1c6c]], [[1c6d]], [[1c6e]], [[1c6f]], [[1c6g]], [[1c6h]], [[1c6i]], [[1c6j]], [[1c6k]], [[1c6l]], [[1c6m]], [[1c6n]], [[1c6p]], [[1c6q]], [[1c6t]] - T4Lys (mutant) + noble gas 
[[3ht6]], [[3ht7]], [[3ht8]], [[3ht9]], [[3htb]], [[3hu8]], [[3huq]], [[3guj]], [[3guk]], [[3gul]], [[3gum]], [[3gun]], [[3guo]], [[3gup]], [[3dmx]], [[3dmz]], [[3dn0]], [[3dn1]], [[3dn2]], [[3dn3]], [[3dn4]], [[3dn6]], [[3dn8]], [[3dna]], [[2rb1]], [[2ray]], [[2raz]], [[2rb0]], [[2rb2]], [[2rbn]], [[2rbo]], [[2rbq]], [[2rbr]], [[2rbs]], [[2oty]],[[2otz]], [[1owy]], [[1owz]], [[1ov5]], [[1ov7]], [[1ovh]], [[1ovj]], [[1ovk]], [[1lgw]], [[1lgx]], [[1li2]], [[1li3]], [[1l83]], [[1l84]] – T4Lys (mutant) + benzene derivative 
[[3htd]], [[3htf]], [[3htg]], [[3hu9]], [[3hua]], [[3huk]], [[3hh3]], [[3hh4]], [[3hh5]], [[3hh6]], [[2rbp]], [[2ou0]], [[2f2q]], [[2f32]], [[2f47]], [[1xep]] – T4Lys (mutant) + inhibitor 
[[148l]] - T4Lys (mutant) + glucoside 
[[3d3d]], [[1d9u]] – lamLys + chitohexasaccharide 
[[1am7]] – lamLys - Enterobacteria phage λ 
[[2anv]], [[2anx]] – Lys (mutant)]] - Enterobacteria phage p22 
[[1xjt]], [[1xju]] - Lys - Enterobacteria phage p1 
[[1lba]] - T7Lys - Enterobacteria phage T7 

===Lys protein complex===

[[3m18]], [[3g3a]], [[3g3b]] - HEWL + Variable lymphocyte receptor – Marine lamprey 
[[3a67]], [[3a6b]], [[3a6c]], [[2yss]], [[2eiz]], [[2dqc]], [[2dqd]], [[2dqe]], [[2dqf]], [[2dqg]], [[2dqh]], [[2dqi]], [[2dqj]], [[1j1o]], [[1j1p]], [[1j1x]], [[1ic4]], [[1ic5]], [[1ic7]] – HEWL + mLys antibody HYHEL-10 (mutant) 
[[1xgp]], [[1xgq]], [[1xgr]], [[1xgt]], [[1xgu]] – HEWL + mLys antibody HYHEL-63 
[[3d9a]], [[2eks]], [[1ua6]], [[1c08]], [[3hfm]] – HEWL + mLys antibody HYHEL-10 
[[1uac]] - tuLys C + mLys antibody HYHEL-10 
[[1yqv]], [[2iff]] – HEWL + mLys antibody HYHEL-5 
[[1bql]] – BqLys + mLys antibody HYHEL-5 
[[1ndg]] – HEWL + mLys antibody HYHEL-8 
[[1ndm]] – HEWL + mLys antibody HYHEL-26 
[[1dqj]] - HEWL + mLys antibody HYHEL-63 
[[1nby]], [[1nbz]] – HEWL (mutant) + mLys antibody HYHEL-63 
[[1g7h]], [[1g7i]], [[1g7j]], [[1g7l]], [[1g7m]], [[1kip]], [[1kiq]], [[1kir]] – HEWL + mAnti-HEWL monoclonal antibody (mutant) 
[[1mlc]], [[1vfb]] - HEWL + mIGG1-κ D44.1 FAB 
[[1a2y]] - HEWL (mutant) + mIGG1-κ D1.3 FV 
[[1fdl]] - HEWL + mIGG1-κ D1.3 FAB 
[[1jhl]] – phLys + mIGG1-κ D11.15 FV 
[[1fbi]] – GfLys + mIGG1 F9.13.7 FAB 
[[2znw]], [[2znx]] – HEWL + hSCFV10 antibody 
[[1bvk]] - HEWL + hAnti Lys FV antibody 
[[1dzb]] – tuLys + mSCFV 1F9 
[[1zv5]], [[1zvh]], [[1zvy]], [[1zmy]], [[1ri8]], [[1rjc]], [[1xfp]], [[1jtp]], [[1jtt]], [[1jto]], [[1mel]] - HEWL + cAntibody heavy chain domain – camel 
[[1op9]] - hLys C + cAntibody heavy chain domain 
[[3otp]] – HEWL + EcProtease DO – ''Escherichia coli'' 
[[3f6z]] - HEWL + MLIC – ''Pseudomonas aeruginosa'' 
[[3eba]] – hLys C + hCABHUL6 
[[2qb0]], [[2qar]] – T4Lys/E80 TELSAM domain 
[[2i25]], [[2i26]] - HEWL +NsAntigen receptor PBLA8 variable domain – Nurse shark 
[[1sq2]], [[1t6v]] – HEWL +NsNew Antigen receptor variable domain 
[[1gpq]] – HEWL + EcInhibitor of Vertebrate Lys 
[[1aro]] – T7Lys + T7 RNA polymerase 

===Some Useful External Links===
[http://en.wikipedia.org/wiki/Lysozyme Lysozyme]

[http://en.wikipedia.org/wiki/Glycoside_hydrolase#Retaining_glycoside_hydrolases Retaining Glycoside Hydrolases]

===References===
<references/>

Hen Egg-White (HEW) Lysozyme

2011-03-31T01:08:38Z

Anne Goodling:

<applet load='aln_1H6M_to_1HEW_2.pdb' size='300' frame='true' align='right' caption=' Hen Egg White (HEW) Lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to the active site, PDBid 1HEW' scene='User:Judy_Voet/Lysozyme/Lysozyme1/16' />
Lysozyme was the first enzyme whose X-ray structure was determined <ref> PMID 5840126</ref><ref>Phillips, D. C. The hen egg white lysozyme molecule. Proc. Natl Acad. Sci. USA 57, 483-495 (1967)</ref>. This <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>scene </scene> shows Hen Egg White (HEW) lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to a cleft in the enzyme. David Phillips, who determined the structure in 1965, saw that the cleft was large enough to fit three more saccharide units. He therefore built a model extending the trisaccharide to a
<scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> that fits into the cleft, labeling the sugar subsites A-F<ref> coordinates of the model kindly provided by Louise Johnson</ref>. Alternately click on <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>trisaccharide</scene> and <scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> to turn the modeled portion of the hexasaccharide on and off.
The interesting thing about the model was that the only way that the hexasaccharide would fit into the cleft was if the 4th saccharide (in subsite D) was strained into a <scene name='User:Judy_Voet/Lysozyme/Half-chair/2'>half-chair conformation</scene>. This conformation is what would be necessary for the formation of an oxocarbenium ion (oxionium ion). When the model was studied, <scene name='User:Judy_Voet/Lysozyme/Glu_35/1'>Glu 35</scene> was found to be in an ideal location to act as a general acid catalyst, 3.34 Angstroms from the bridging oxygen between the 4th and 5th saccharide units. <scene name='User:Judy_Voet/Lysozyme/Asp_52/2'>Asp 52</scene> appeared to be too far away (2.69 angstroms) in the static lysozyme structure to have formed a covalent bond with C1 of the half-chair model in the D site, and no covalent intermediate had ever been detected, so Phillips proposed that it acted as an electrostatic stabilizer of the oxonium ion (referred to as The Phillips Mechanism).

Then, in 2001, Stephen Withers published <scene name='User:Judy_Voet/Lysozyme/1h6m/3'>1H6M</scene>,<ref>PMID 11518970</ref> in which Glu 35 had been mutated to Gln to remove the general acid catalyst. The substrate contained NAG-2-fluoro-glucosyl fluoride (NAG2FGlcF). The fluoro group on C-1 does not require acid catalysis to be a good leaving group, and the remaining saccharide, in the absence of the acid necessary to catalyse the second step of the reaction, was demonstrated to form a <scene name='User:Judy_Voet/Lysozyme/Covalent/1'> covalent intermediate</scene>. In this <scene name='User:Judy_Voet/Lysozyme/Superposition/2'>superposition</scene> of the half chair model with 1HEW (greens) and the covalent intermediate in 1H6M (blues), note the relatively small motions of Asp 52 and C1 of the sugar ring in going from the model to the covalent intermediate. to observe the motion from the <scene name='User:Judy_Voet/Lysozyme/Asp52_halfchair/1'>half-chair</scene> to the <scene name='User:Judy_Voet/Lysozyme/Covalent/2'>covalent intermediate</scene> just toggle between the two green links.

<applet load='aln_1H6M_to_1HEW_2.pdb' size='300' frame='true' align='right' caption='NAG-2-deoxy-2-fluoro-glucosyl fluoride (NAG2FGlcF) bound to Glu35Gln HEW Lysozyme PDBid 1H6M' scene='User:Judy_Voet/Lysozyme/1h6m/3'/>

== 3D Structures of Lysozyme ==

===Lys===

[[2x0a]], [[3iju]], [[3ijv]], [[3a8z]], [[2w1y]], [[2w1m]], [[2w1x]], [[2w1l]], [[3e3d]], [[3exd]], [[2zq3]], [[2zq4]], [[3b72]], [[3b6l]], [[2z12]], [[2z18]], [[2z19]], [[2vb1]], [[2hu3]], [[2hub]], [[2htx]], [[2hu1]], [[2yvb]], [[2epe]], [[2g4p]], [[2g4q]], [[2cgi]], [[2b5z]], [[2d4k]], [[2d91]], [[2f2n]], [[2fbb]], [[2c8o]], [[2c8p]], [[2a6u]], [[2aub]], [[2blx]], [[2bly]], [[2a7d]], [[2a7f]], [[1wtm]], [[1wtn]], [[1w6z]], [[1vdp]], [[1vdq]], [[1vds]], [[1vdt]], [[1ved]], [[1v7t]], [[1ps5]], [[2cds]], [[1lj3]], [[1lj4]], [[1lje]], [[1ljf]], [[1ljg]], [[1ljh]], [[1lji]], [[1ljj]], [[1ljk]], [[1jis]], [[1jit]], [[1jiy]], [[1jj0]], [[1jj1]], [[1jj3]], [[1iee]], [[1qio]], [[1f0w]], [[1f10]], [[1dpx]], [[1c10]], [[1qtk]], [[1lz8]], [[1lz9]], [[1bhz]], [[1bgi]], [[1bwh]], [[1bwi]], [[1bwj]], [[1bvx]], [[1hsw]], [[1hsx]], [[1lpi]], [[4lzt]], [[3lzt]], [[1aki]], [[1jpo]], [[1rfp]], [[193l]], [[194l]], [[5lym]], [[1lza]], [[3lyt]], [[4lyt]], [[5lyt]], [[6lyt]], [[2lzt]], [[1lzt]], [[1lzh]], [[2lzh]], [[7lyz]], [[1lyz]], [[2lyz]], [[3lyz]], [[4lyz]], [[5lyz]], [[6lyz]] - HEWL – chicken 
[[1xei]], [[1xej]], [[1xek]], [[1uco]], [[1lma]], [[4lym]] – HEWL low hydration 
[[1lsa]], [[1lsb]], [[1lsc]], [[1lsd]], [[1lse]], [[1lsf]], [[1lys]] – HEWL temperature influence 
[[2lym]], [[3lym]] – HEWL pressure influence 
[[132l]] – HEWL methylated 
[[1rcm]] – HEWL 3 S-S form 
[[2xbr]], [[2xbs]]- HEWL– Raman crystallography 
[[2zwb]], [[1io5]], [[1lzn]] - HEWL– Neutron 
[[1gxv]], [[1gxx]], [[1e8l]] - HEWL- NMR 
[[2hs7]], [[2hso]], [[2hs9]]- HEWL– Powder diffraction 
[[1ir7]], [[1ir8]], [[1ir9]], [[1ioq]], [[1ior]], [[1ios]], [[1iot]], [[1flq]], [[1flu]], [[1flw]], [[1fly]], [[1fn5]], [[1kxw]], [[1kxx]], [[1kxy]], [[1uia]], [[1uib]], [[1uic]], [[1uid]], [[1uie]], [[1uif]], [[1uig]], [[1uih]], [[1lsm]], [[1lsn]], [[1hel]], [[1hem]], [[1hen]], [[1heo]], [[1hep]], [[1heq]], [[1her]] – HEWL (mutant) 
[[1lyo]], [[2lyo]], [[3lyo]], [[4lyo]] – HEWL cross-linked 
[[1xft]] - tuLys – turkey - Powder diffraction 
[[1jse]], [[1tew]], [[135l]], [[2lz2]], [[1lz2]] – tuLys 
[[3lz2]] – tuLys - Laue 
[[3ab6]] – Lys + NAG3 – Hard clam 
[[2x8r]] – Lys GH25 – ''Aspergillus fumigatus'' 
[[3mgw]] – Lys G – Atlantic salmon 
[[3gxk]], [[3gxr]] – Lys G + NAG – Atlantic cod 
[[2fbd]] – HfLys 1 
[[3cb7]] – HfLys 2 
[[2zij]], [[2zik]], [[2zil]], [[2nwd]], [[1iwt]], [[1iwu]], [[1iwv]], [[1iww]], [[1iwx]], [[1iwy]], [[1iwz]], [[1jwr]], [[1jsf]], [[1rex]], [[1lz1]] – hLys – human 
[[1w08]], [[1ix0]], [[1ioc]], [[1ip1]], [[1ip2]], [[1ip3]], [[1ip4]], [[1ip5]], [[1ip6]], [[1ip7]], [[1qsw]], [[1gev]], [[1gez]], [[1gf0]], [[1gf3]], [[1gf4]], [[1gf5]], [[1gf6]], [[1gf7]], [[1i1z]], [[1i20]], [[1i22]], [[1gfr]], [[1gft]], [[1gfu]], [[1gfv]], [[1gf8]], [[1gf9]], [[1gfa]], [[1gfe]], [[1gfg]], [[1gfh]], [[1gfj]], [[1gfk]], [[1inu]], [[1gdx]], [[1ge0]], [[1ge1]], [[1ge2]], [[1ge3]], [[1ge4]], [[1gdw]], [[1gaz]], [[1gb0]], [[1gb2]], [[1gb3]], [[1gb5]], [[1gb6]], [[1gb7]], [[1gb8]], [[1gb9]], [[1gbo]], [[1gbw]], [[1gbx]], [[1gby]], [[1gbz]], [[1gay]], [[1eq4]], [[1eq5]], [[1eqe]], [[1c7p]], [[1di3]], [[1di4]], [[1di5]], [[1c43]], [[1c45]], [[1c46]], [[1ckg]], [[1cj6]], [[1cj7]], [[1cj8]], [[1cj9]], [[1ckc]], [[1ckd]], [[1ckf]], [[1ckh]], [[1b5z]], [[1b70]], [[1b7q]], [[1b7r]], [[1b7s]], [[1b7l]], [[1b7m]], [[1b7n]], [[1b7p]], [[1b5u]], [[1b5v]], [[1b5w]], [[1b5x]], [[1b5y]], [[1bb3]], [[1bb4]], [[2bqa]], [[2bqb]], [[2bqc]], [[2bqd]], [[2bqe]], [[2bqf]], [[2bqg]], [[2bqh]], [[2bqi]], [[2bqj]], [[2bqk]], [[2bql]], [[2bqm]], [[2bqn]], [[2bqo]], [[2mea]], [[2meb]], [[2mec]], [[2med]], [[2mee]], [[2mef]], [[2meg]], [[2meh]], [[2mei]], [[1wqm]], [[1wqn]], [[1wqo]], [[1wqp]], [[1wqq]], [[1wqr]], [[2heb]], [[2hea]], [[2hec]], [[2hed]], [[2hee]], [[2hef]], [[1jka]], [[1jkb]], [[1jkc]], [[1jkd]], [[1loz]], [[1lyy]], [[1oua]], [[1oub]], [[1ouc]], [[1oud]], [[1oue]], [[1ouf]], [[1oug]], [[1ouh]], [[1oui]], [[1ouj]], [[207l]], [[208l ]], [[1yam]], [[1yan]], [[1yao]], [[1yap]], [[1yaq]], [[1lmt]], [[1lhh]], [[1lhi]], [[1lhj]], [[1lhk]], [[1lhl]], [[133l]], [[134l]], [[1lz4]], [[1lz5]], [[1lz6]], [[1laa]], [[1tay]], [[1tby]], [[1tcy]], [[1tdy]], [[2lhm]], [[3lhm]] – hLys (mutant) 
[[1iy3]], [[1iy4]] – hLys - NMR 
[[2z2f]] – Lys – Bovine 
[[2cwi]], [[1el1]], [[1qqy]] – dLys - dog 
[[2z2e]] – dLys (mutant) 
[[1i56]] – dLys – NMR 
[[2dqa]] – Lys – ''Tapes japonica'' 
[[2gv0]] – Lys – Soft-shelled turtle 
[[1ivm]] – mLys M – NMR – mouse 
[[1jfx]] – Lys – ''Streptomyces coelicolor'' 
[[1gd6]] – Lys – ''Bombyx mori'' 
[[1jug]] – Lys – Echidna 
[[1dkj]] – BqLys – Bobwhite quail 
[[2ihl]] – Lys – Japanese quail 
[[1gbs]] – BsLys – Black swan 
[[1lmn]] – RtLys – Rainbow trout 
[[2eql]] – Lys – horse 
[[1ghl]] – phLys – pheasant 
[[1hhl]] – GfLys – Guinea fowl 
[[1lhm]] – Lys (mutant) – yeast 

===Lys small molecules complexes===

[[3fe0]], [[2d4i]], [[2d4j]], [[1v7s]] - HEWL+ D2O 
[[3m3u]] – HEWL Trp fluorescence 
[[2xjw]] - HEWL + CO 
[[1hf4]], [[1lks]] – HEWL + NO3 
[[3a34]], [[3ems]] - HEWL + arginine 
[[2xth]] – cLys + inhibitor K2PtBr6 
[[3a90]], [[3a91]], [[3a92]], [[3a93]], [[3a94]], [[3a95]], [[3a96]], [[3kam]], [[2pc2]], [[2bpu]], [[1t3p]], [[1h87]] – HEWL + rare earth 
[[2d6b]], [[2hg0]], [[1vat]], [[1gwd]], [[1b2k]], [[1lkr]], [[1azf]], [[8lyz]]- HEWL+ halogen 
[[1vat]] - HEWL + Xe 
[[1n4f]] - HEWL + As 
[[2i6z]] - HEWL + Pt drug 
[[2zyp]] - HEWL + poly (allyl amine) 
[[2f30]], [[2f4a]] – HEWL + urea derivative 
[[2f4g]], [[1ykx]], [[1yky]], [[1ykz]], [[1yl0]], [[1yl1]], [[1z55]] - HEWL + alcohol 
[[1dpw]] – HEWL + MPD 
[[1lcn]] – HEWL + SCN 
[[2zxs]] - HEWL with glycine-amide 
[[2h9j]], [[2h9k]], [[1yik]], [[1yil]] - HEWL + cyclam derivative 
[[1b0d]] – HEWL + p-toluene-sulfonate 
[[2q0m]] - HEWL + tricarbonylmanganese 
[[2war]] – HEWL (mutant) + chitopentaose 
[[2h5z]] – HfLys 1 + chitotetraose – House fly 
[[1hnl]] – hLys + glutathione 
[[1dkk]] – BqLys + NO3 

===Lys complex with glucoside===

[[3a3q]] – HEWL (mutant) + NAG 
[[1sf4]], [[1sf6]], [[1sf7]], [[1sfb]], [[1sfg]], [[1ja2]], [[1ja4]], [[1ja6]], [[1ja7]] – HEWL + NAG oligosaccharide – Powder diffraction 
[[1ubz]], [[1d6p]], [[1d6q]], [[1bb5]] – hLys (mutant) + glycoside 
[[1uc0]], [[1re2]], [[1rem]], [[1rey]], [[1rez]], [[1lzr]], [[1lzs]] - hLys + glycoside 
[[1ljn]], [[1jef]], [[1lzy]] – tuLys + glycoside 
[[1h6m]], [[1at5]], [[1at6]], [[1lzb]], [[1lzc]], [[1lzd]], [[1lze]], [[1lzg]], [[1hew ]]– HEWL + glycoside 
[[1lsy]], [[1lsz]] - HEWL (mutant) + glycoside 
[[1bb6]], [[1bb7]] – RtLys + glycoside 
[[1lmc]] – RtLys + bulgecin 
[[1lmo]], [[1lmp]], [[1lmq]] – RtLys + glucoside 
[[1lsp]] – BsLys + bulgecin 
[[153l]], [[154l]] – Lys +glucoside – goose 

===Phage Lys===

[[2oe4]], [[2oe7]], [[2oe9]], [[2oea]], [[1swz]], [[1cx6]], [[1qtc]], [[1qtd]], [[1qth]], [[1qsb]], [[1qs5]], [[1qs9]], [[1qtb]], [[256l]], [[206l]], [[167l]], [[168l]], [[169l]], [[170l]], [[171l]], [[172l]], [[173l]], [[174l]], [[175l]], [[176l]], [[177l]], [[178l]], [[181l]], [[182l]], [[183l]], [[184l]], [[185l]], [[186l]], [[187l]], [[188l]], [[1nhb]], [[137l]], [[216l]], [[152l]], [[149l]], [[150l]], [[151l]], [[1lyd]], [[2lzm]] - T4Lys – Enterobacteria phage T4 
[[138l]] – T4Lys cross-linked 
[[4lzm]], [[5lzm]], [[6lzm]], [[7lzm]] – T4Lys ionic strength 
[[3l2x]], [[3k2r]], [[3g3v]], [[3g3w]], [[3g3x]], [[2q9d]], [[2q9e]], [[2igc]], [[2ntg]], [[2nth]], [[2ou8]], [[2ou9]], [[1zur]], [[1zwn]], [[1zyt]], [[2cuu]], [[2a4t]] – T4Lys (mutant) spin labeled 
[[3l64]], [[3hwl]], [[3jr6]], [[3gui]], [[3c7w]], [[3c7y]], [[3c7z]], [[3c80]], [[3c81]], [[3c82]], [[3c83]], [[3c8q]], [[3c8r]], [[3c8s]], [[3cdo]], [[3cdq]], [[3cdr]], [[3cdt]], [[3cdv]], [[3f8v]], [[3f9l]], [[3fa0]], [[3fad]], [[3fi5]], [[3dke]], [[3dmv]], [[2o4w]], [[2o79]], [[2o7a]], [[2huk]], [[2hul]], [[2hum]], [[2b7x]], [[2b6t]], [[2b6w]], [[2b6x]], [[2b6y]], [[2b6z]], [[2b70]], [[2b72]], [[2b73]], [[2b74]], [[2b75]], [[1sx7]], [[1swy]], [[1sx2]], [[1t6h]], [[1ssw]], [[1ssy]], [[1t8f]], [[1t8g]], [[1t8a]], [[1t97]], [[1p56]], [[1p5c]], [[1p2l]], [[1p2r]], [[1p36]], [[1p37]], [[1p3n]], [[1p46]], [[1p64]], [[1p6y]], [[1p7s]], [[1pqd]], [[1pqi]], [[1pqj]], [[1pqk]], [[1pqm]], [[1pqo]], [[1oyu]], [[1ks3]], [[1kw5]], [[1kw7]], [[1ky0]], [[1ky1]], [[1l0j]], [[1l0k]], [[1lw9]], [[1lwg]], [[1lwk]], [[1lpy]], [[1llh]], [[1lgu]], [[1li6]], [[1jtm]], [[1jtn]], [[1jqu]], [[1kni]], [[1g06]], [[1g07]], [[1g0g]], [[1g0j]], [[1g0k]], [[1g0l]], [[1g0m]], [[1g0p]], [[1g0q]], [[1g1v]], [[1g1w]], [[1i6s]], [[257l]], [[258l]], [[260l]], [[1epy]], [[1b6i]], [[1cu6]], [[1d9w]], [[1ctw]], [[1cu0]], [[1cu2]], [[1cu3]], [[1cu5]], [[1cv1]], [[1cv4]], [[1cv5]], [[1cv6]], [[1cvk]], [[1cx7]], [[1d2w]], [[1d2y]], [[1d3f]], [[1d3j]], [[1d3m]], [[1d3n]], [[1cv3]], [[1qt3]], [[1qt4]], [[1qt5]], [[1qt6]], [[1qt7]], [[1qt8]], [[1qtv]], [[1qtz]], [[1qud]], [[1qug]], [[1quh]], [[1quo]], [[1qsq]], [[261l]], [[262l]], [[259l]], [[220l]], [[222l]], [[223l]], [[225l]], [[226l]], [[227l]], [[228l]], [[229l]], [[235l]], [[236l]], [[237l]], [[238l]], [[239l]], [[240l]], [[241l]], [[242l]], [[243l]], [[244l]], [[245l]], [[246l]], [[247l]], [[248l]], [[249l]], [[250l]], [[251l]], [[252l]], [[253l]], [[254l]], [[255l]], [[230l]], [[231l]], [[232l]], [[233l]], [[234l]], [[209l]], [[210l]], [[211l]], [[212l]], [[213l]], [[214l]], [[215l]], [[218l]], [[219l]], [[180l]], [[195l]], [[196l]], [[197l]], [[198l]], [[199l]], [[200l]], [[190l]], [[191l]], [[192l]], [[189l]], [[155l]], [[156l]], [[157l]], [[158l]], [[159l]], [[160l]], [[161l]], [[162l]], [[163l]], [[164l]], [[165l]], [[166l]], [[129l]], [[130l]], [[131l]], [[140l]], [[141l]], [[142l]], [[143l]], [[144l]], [[145l]], [[146l]], [[147l]], [[201l]], [[205l]], [[221l]], [[224l]], [[102l]], [[103l]], [[104l]], [[107l]], [[108l]], [[109l]], [[110l]], [[111l]], [[112l]], [[113l]], [[114l]], [[115l]], [[118l]], [[119l]], [[120l]], [[122l]], [[123l]], [[125l]], [[126l]], [[127l]], [[128l]], [[1dya]], [[1dyb]], [[1dyc]], [[1dyd]], [[1dye]], [[1dyf]], [[1dyg]], [[1l00]], [[1l85]], [[1l86]], [[1l87]], [[1l88]], [[1l89]], [[1l90]], [[1l91]], [[1l92]], [[1l93]], [[1l94]], [[1l95]], [[1l96]], [[1l97]], [[1l98]], [[1l99]], [[1lye]], [[1lyf]], [[1lyg]], [[1lyh]], [[1lyi]], [[1lyj]], [[217l]], [[1tla]], [[1l77]], [[1l79]], [[1l80]], [[1l81]], [[1l82]], [[2l78]], [[1l36]], [[1l37]], [[1l38]], [[1l39]], [[1l40]], [[1l41]], [[1l42]], [[1l43]], [[1l44]], [[1l45]], [[1l46]], [[1l47]], [[1l48]], [[1l49]], [[1l50]], [[1l51]], [[1l52]], [[1l53]], [[1l54]], [[1l55]], [[1l56]], [[1l57]], [[1l58]], [[1l59]], [[1l60]], [[1l61]], [[1l62]], [[1l63]], [[1l64]], [[1l65]], [[1l66]], [[1l67]], [[1l68]], [[1l69]], [[1l70]], [[1l71]], [[1l72]], [[1l73]], [[1l74]], [[1l75]], [[1l76]], [[1l17]], [[1l18]], [[1l19]], [[1l20]], [[1l21]], [[1l22]], [[1l23]], [[1l24]], [[1l25]], [[1l26]], [[1l27]], [[1l28]], [[1l29]], [[1l30]], [[1l31]], [[1l32]], [[1l33]], [[1l34]], [[1l35]], [[3lzm]], [[1l01]], [[1l02]], [[1l03]], [[1l04]], [[1l05]], [[1l06]], [[1l07]], [[1l08]], [[1l09]], [[1l10]], [[1l11]], [[1l12]], [[1l13]], [[1l14]], [[1l15]], [[1l16]] – T4Lys (mutant) 
[[1c60]], [[1c61]], [[1c62]], [[1c63]], [[1c64]], [[1c65]], [[1c66]], [[1c67]], [[1c68]], [[1c69]], [[1c6a]], [[1c6b]], [[1c6c]], [[1c6d]], [[1c6e]], [[1c6f]], [[1c6g]], [[1c6h]], [[1c6i]], [[1c6j]], [[1c6k]], [[1c6l]], [[1c6m]], [[1c6n]], [[1c6p]], [[1c6q]], [[1c6t]] - T4Lys (mutant) + noble gas 
[[3ht6]], [[3ht7]], [[3ht8]], [[3ht9]], [[3htb]], [[3hu8]], [[3huq]], [[3guj]], [[3guk]], [[3gul]], [[3gum]], [[3gun]], [[3guo]], [[3gup]], [[3dmx]], [[3dmz]], [[3dn0]], [[3dn1]], [[3dn2]], [[3dn3]], [[3dn4]], [[3dn6]], [[3dn8]], [[3dna]], [[2rb1]], [[2ray]], [[2raz]], [[2rb0]], [[2rb2]], [[2rbn]], [[2rbo]], [[2rbq]], [[2rbr]], [[2rbs]], [[2oty]],[[2otz]], [[1owy]], [[1owz]], [[1ov5]], [[1ov7]], [[1ovh]], [[1ovj]], [[1ovk]], [[1lgw]], [[1lgx]], [[1li2]], [[1li3]], [[1l83]], [[1l84]] – T4Lys (mutant) + benzene derivative 
[[3htd]], [[3htf]], [[3htg]], [[3hu9]], [[3hua]], [[3huk]], [[3hh3]], [[3hh4]], [[3hh5]], [[3hh6]], [[2rbp]], [[2ou0]], [[2f2q]], [[2f32]], [[2f47]], [[1xep]] – T4Lys (mutant) + inhibitor 
[[148l]] - T4Lys (mutant) + glucoside 
[[3d3d]], [[1d9u]] – lamLys + chitohexasaccharide 
[[1am7]] – lamLys - Enterobacteria phage λ 
[[2anv]], [[2anx]] – Lys (mutant)]] - Enterobacteria phage p22 
[[1xjt]], [[1xju]] - Lys - Enterobacteria phage p1 
[[1lba]] - T7Lys - Enterobacteria phage T7 

===Lys protein complex===

[[3m18]], [[3g3a]], [[3g3b]] - HEWL + Variable lymphocyte receptor – Marine lamprey 
[[3a67]], [[3a6b]], [[3a6c]], [[2yss]], [[2eiz]], [[2dqc]], [[2dqd]], [[2dqe]], [[2dqf]], [[2dqg]], [[2dqh]], [[2dqi]], [[2dqj]], [[1j1o]], [[1j1p]], [[1j1x]], [[1ic4]], [[1ic5]], [[1ic7]] – HEWL + mLys antibody HYHEL-10 (mutant) 
[[1xgp]], [[1xgq]], [[1xgr]], [[1xgt]], [[1xgu]] – HEWL + mLys antibody HYHEL-63 
[[3d9a]], [[2eks]], [[1ua6]], [[1c08]], [[3hfm]] – HEWL + mLys antibody HYHEL-10 
[[1uac]] - tuLys C + mLys antibody HYHEL-10 
[[1yqv]], [[2iff]] – HEWL + mLys antibody HYHEL-5 
[[1bql]] – BqLys + mLys antibody HYHEL-5 
[[1ndg]] – HEWL + mLys antibody HYHEL-8 
[[1ndm]] – HEWL + mLys antibody HYHEL-26 
[[1dqj]] - HEWL + mLys antibody HYHEL-63 
[[1nby]], [[1nbz]] – HEWL (mutant) + mLys antibody HYHEL-63 
[[1g7h]], [[1g7i]], [[1g7j]], [[1g7l]], [[1g7m]], [[1kip]], [[1kiq]], [[1kir]] – HEWL + mAnti-HEWL monoclonal antibody (mutant) 
[[1mlc]], [[1vfb]] - HEWL + mIGG1-κ D44.1 FAB 
[[1a2y]] - HEWL (mutant) + mIGG1-κ D1.3 FV 
[[1fdl]] - HEWL + mIGG1-κ D1.3 FAB 
[[1jhl]] – phLys + mIGG1-κ D11.15 FV 
[[1fbi]] – GfLys + mIGG1 F9.13.7 FAB 
[[2znw]], [[2znx]] – HEWL + hSCFV10 antibody 
[[1bvk]] - HEWL + hAnti Lys FV antibody 
[[1dzb]] – tuLys + mSCFV 1F9 
[[1zv5]], [[1zvh]], [[1zvy]], [[1zmy]], [[1ri8]], [[1rjc]], [[1xfp]], [[1jtp]], [[1jtt]], [[1jto]], [[1mel]] - HEWL + cAntibody heavy chain domain – camel 
[[1op9]] - hLys C + cAntibody heavy chain domain 
[[3otp]] – HEWL + EcProtease DO – ''Escherichia coli'' 
[[3f6z]] - HEWL + MLIC – ''Pseudomonas aeruginosa'' 
[[3eba]] – hLys C + hCABHUL6 
[[2qb0]], [[2qar]] – T4Lys/E80 TELSAM domain 
[[2i25]], [[2i26]] - HEWL +NsAntigen receptor PBLA8 variable domain – Nurse shark 
[[1sq2]], [[1t6v]] – HEWL +NsNew Antigen receptor variable domain 
[[1gpq]] – HEWL + EcInhibitor of Vertebrate Lys 
[[1aro]] – T7Lys + T7 RNA polymerase 

===Some Useful External Links===
[http://en.wikipedia.org/wiki/Lysozyme Lysozyme]

[http://en.wikipedia.org/wiki/Glycoside_hydrolase#Retaining_glycoside_hydrolases Retaining Glycoside Hydrolases]

===References===
<references/>

Hen Egg-White (HEW) Lysozyme

2011-03-31T01:07:39Z

Anne Goodling:

<applet load='aln_1H6M_to_1HEW_2.pdb' size='300' frame='true' align='right' caption=' Hen Egg White (HEW) Lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to the active site, PDBid 1HEW' scene='User:Judy_Voet/Lysozyme/Lysozyme1/16' />
Lysozyme was the first enzyme whose X-ray structure was determined <ref> PMID 5840126</ref><ref>Phillips, D. C. The hen egg white lysozyme molecule. Proc. Natl Acad. Sci. USA 57, 483-495 (1967)</ref>. This <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>scene </scene> shows Hen Egg White (HEW) lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to a cleft in the enzyme. David Phillips, who determined the structure in 1965, saw that the cleft was large enough to fit three more saccharide units. He therefore built a model extending the trisaccharide to a
<scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> that fits into the cleft, labeling the sugar subsites A-F<ref> coordinates of the model kindly provided by Louise Johnson</ref>. Alternately click on <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>trisaccharide</scene> and <scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> to turn the modeled portion of the hexasaccharide on and off.
The interesting thing about the model was that the only way that the hexasaccharide would fit into the cleft was if the 4th saccharide (in subsite D) was strained into a <scene name='User:Judy_Voet/Lysozyme/Half-chair/2'>half-chair conformation</scene>. This conformation is what would be necessary for the formation of an oxocarbenium ion (oxionium ion). When the model was studied, <scene name='User:Judy_Voet/Lysozyme/Glu_35/1'>Glu 35</scene> was found to be in an ideal location to act as a general acid catalyst, 3.34 Angstroms from the bridging oxygen between the 4th and 5th saccharide units. <scene name='User:Judy_Voet/Lysozyme/Asp_52/2'>Asp 52</scene> appeared to be too far away (2.69 angstroms) in the static lysozyme structure to have formed a covalent bond with C1 of the half-chair model in the D site, and no covalent intermediate had ever been detected, so Phillips proposed that it acted as an electrostatic stabilizer of the oxonium ion (referred to as The Phillips Mechanism).

Then, in 2001, Stephen Withers published <scene name='User:Judy_Voet/Lysozyme/1h6m/3'>1H6M</scene>,<ref>PMID 11518970</ref> in which Glu 35 had been mutated to Gln to remove the general acid catalyst. The substrate contained NAG-2-fluoro-glucosyl fluoride (NAG2FGlcF). The fluoro group on C-1 does not require acid catalysis to be a good leaving group, and the remaining saccharide, in the absence of the acid necessary to catalyse the second step of the reaction, was demonstrated to form a <scene name='User:Judy_Voet/Lysozyme/Covalent/1'> covalent intermediate</scene>. In this <scene name='User:Judy_Voet/Lysozyme/Superposition/2'>superposition</scene> of the half chair model with 1HEW (greens) and the covalent intermediate in 1H6M (blues), note the relatively small motions of Asp 52 and C1 of the sugar ring in going from the model to the covalent intermediate. to observe the motion from the <scene name='User:Judy_Voet/Lysozyme/Asp52_halfchair/1'>half-chair</scene> to the <scene name='User:Judy_Voet/Lysozyme/Covalent/2'>covalent intermediate</scene> just toggle between the two green links.
<applet load='aln_1H6M_to_1HEW_2.pdb' size='300' frame='true' align='right' caption='NAG-2-deoxy-2-fluoro-glucosyl fluoride (NAG2FGlcF) bound to Glu35Gln HEW Lysozyme PDBid 1H6M' scene='User:Judy_Voet/Lysozyme/1h6m/3'/>

== 3D Structures of Lysozyme ==

===Lys===

[[2x0a]], [[3iju]], [[3ijv]], [[3a8z]], [[2w1y]], [[2w1m]], [[2w1x]], [[2w1l]], [[3e3d]], [[3exd]], [[2zq3]], [[2zq4]], [[3b72]], [[3b6l]], [[2z12]], [[2z18]], [[2z19]], [[2vb1]], [[2hu3]], [[2hub]], [[2htx]], [[2hu1]], [[2yvb]], [[2epe]], [[2g4p]], [[2g4q]], [[2cgi]], [[2b5z]], [[2d4k]], [[2d91]], [[2f2n]], [[2fbb]], [[2c8o]], [[2c8p]], [[2a6u]], [[2aub]], [[2blx]], [[2bly]], [[2a7d]], [[2a7f]], [[1wtm]], [[1wtn]], [[1w6z]], [[1vdp]], [[1vdq]], [[1vds]], [[1vdt]], [[1ved]], [[1v7t]], [[1ps5]], [[2cds]], [[1lj3]], [[1lj4]], [[1lje]], [[1ljf]], [[1ljg]], [[1ljh]], [[1lji]], [[1ljj]], [[1ljk]], [[1jis]], [[1jit]], [[1jiy]], [[1jj0]], [[1jj1]], [[1jj3]], [[1iee]], [[1qio]], [[1f0w]], [[1f10]], [[1dpx]], [[1c10]], [[1qtk]], [[1lz8]], [[1lz9]], [[1bhz]], [[1bgi]], [[1bwh]], [[1bwi]], [[1bwj]], [[1bvx]], [[1hsw]], [[1hsx]], [[1lpi]], [[4lzt]], [[3lzt]], [[1aki]], [[1jpo]], [[1rfp]], [[193l]], [[194l]], [[5lym]], [[1lza]], [[3lyt]], [[4lyt]], [[5lyt]], [[6lyt]], [[2lzt]], [[1lzt]], [[1lzh]], [[2lzh]], [[7lyz]], [[1lyz]], [[2lyz]], [[3lyz]], [[4lyz]], [[5lyz]], [[6lyz]] - HEWL – chicken 
[[1xei]], [[1xej]], [[1xek]], [[1uco]], [[1lma]], [[4lym]] – HEWL low hydration 
[[1lsa]], [[1lsb]], [[1lsc]], [[1lsd]], [[1lse]], [[1lsf]], [[1lys]] – HEWL temperature influence 
[[2lym]], [[3lym]] – HEWL pressure influence 
[[132l]] – HEWL methylated 
[[1rcm]] – HEWL 3 S-S form 
[[2xbr]], [[2xbs]]- HEWL– Raman crystallography 
[[2zwb]], [[1io5]], [[1lzn]] - HEWL– Neutron 
[[1gxv]], [[1gxx]], [[1e8l]] - HEWL- NMR 
[[2hs7]], [[2hso]], [[2hs9]]- HEWL– Powder diffraction 
[[1ir7]], [[1ir8]], [[1ir9]], [[1ioq]], [[1ior]], [[1ios]], [[1iot]], [[1flq]], [[1flu]], [[1flw]], [[1fly]], [[1fn5]], [[1kxw]], [[1kxx]], [[1kxy]], [[1uia]], [[1uib]], [[1uic]], [[1uid]], [[1uie]], [[1uif]], [[1uig]], [[1uih]], [[1lsm]], [[1lsn]], [[1hel]], [[1hem]], [[1hen]], [[1heo]], [[1hep]], [[1heq]], [[1her]] – HEWL (mutant) 
[[1lyo]], [[2lyo]], [[3lyo]], [[4lyo]] – HEWL cross-linked 
[[1xft]] - tuLys – turkey - Powder diffraction 
[[1jse]], [[1tew]], [[135l]], [[2lz2]], [[1lz2]] – tuLys 
[[3lz2]] – tuLys - Laue 
[[3ab6]] – Lys + NAG3 – Hard clam 
[[2x8r]] – Lys GH25 – ''Aspergillus fumigatus'' 
[[3mgw]] – Lys G – Atlantic salmon 
[[3gxk]], [[3gxr]] – Lys G + NAG – Atlantic cod 
[[2fbd]] – HfLys 1 
[[3cb7]] – HfLys 2 
[[2zij]], [[2zik]], [[2zil]], [[2nwd]], [[1iwt]], [[1iwu]], [[1iwv]], [[1iww]], [[1iwx]], [[1iwy]], [[1iwz]], [[1jwr]], [[1jsf]], [[1rex]], [[1lz1]] – hLys – human 
[[1w08]], [[1ix0]], [[1ioc]], [[1ip1]], [[1ip2]], [[1ip3]], [[1ip4]], [[1ip5]], [[1ip6]], [[1ip7]], [[1qsw]], [[1gev]], [[1gez]], [[1gf0]], [[1gf3]], [[1gf4]], [[1gf5]], [[1gf6]], [[1gf7]], [[1i1z]], [[1i20]], [[1i22]], [[1gfr]], [[1gft]], [[1gfu]], [[1gfv]], [[1gf8]], [[1gf9]], [[1gfa]], [[1gfe]], [[1gfg]], [[1gfh]], [[1gfj]], [[1gfk]], [[1inu]], [[1gdx]], [[1ge0]], [[1ge1]], [[1ge2]], [[1ge3]], [[1ge4]], [[1gdw]], [[1gaz]], [[1gb0]], [[1gb2]], [[1gb3]], [[1gb5]], [[1gb6]], [[1gb7]], [[1gb8]], [[1gb9]], [[1gbo]], [[1gbw]], [[1gbx]], [[1gby]], [[1gbz]], [[1gay]], [[1eq4]], [[1eq5]], [[1eqe]], [[1c7p]], [[1di3]], [[1di4]], [[1di5]], [[1c43]], [[1c45]], [[1c46]], [[1ckg]], [[1cj6]], [[1cj7]], [[1cj8]], [[1cj9]], [[1ckc]], [[1ckd]], [[1ckf]], [[1ckh]], [[1b5z]], [[1b70]], [[1b7q]], [[1b7r]], [[1b7s]], [[1b7l]], [[1b7m]], [[1b7n]], [[1b7p]], [[1b5u]], [[1b5v]], [[1b5w]], [[1b5x]], [[1b5y]], [[1bb3]], [[1bb4]], [[2bqa]], [[2bqb]], [[2bqc]], [[2bqd]], [[2bqe]], [[2bqf]], [[2bqg]], [[2bqh]], [[2bqi]], [[2bqj]], [[2bqk]], [[2bql]], [[2bqm]], [[2bqn]], [[2bqo]], [[2mea]], [[2meb]], [[2mec]], [[2med]], [[2mee]], [[2mef]], [[2meg]], [[2meh]], [[2mei]], [[1wqm]], [[1wqn]], [[1wqo]], [[1wqp]], [[1wqq]], [[1wqr]], [[2heb]], [[2hea]], [[2hec]], [[2hed]], [[2hee]], [[2hef]], [[1jka]], [[1jkb]], [[1jkc]], [[1jkd]], [[1loz]], [[1lyy]], [[1oua]], [[1oub]], [[1ouc]], [[1oud]], [[1oue]], [[1ouf]], [[1oug]], [[1ouh]], [[1oui]], [[1ouj]], [[207l]], [[208l ]], [[1yam]], [[1yan]], [[1yao]], [[1yap]], [[1yaq]], [[1lmt]], [[1lhh]], [[1lhi]], [[1lhj]], [[1lhk]], [[1lhl]], [[133l]], [[134l]], [[1lz4]], [[1lz5]], [[1lz6]], [[1laa]], [[1tay]], [[1tby]], [[1tcy]], [[1tdy]], [[2lhm]], [[3lhm]] – hLys (mutant) 
[[1iy3]], [[1iy4]] – hLys - NMR 
[[2z2f]] – Lys – Bovine 
[[2cwi]], [[1el1]], [[1qqy]] – dLys - dog 
[[2z2e]] – dLys (mutant) 
[[1i56]] – dLys – NMR 
[[2dqa]] – Lys – ''Tapes japonica'' 
[[2gv0]] – Lys – Soft-shelled turtle 
[[1ivm]] – mLys M – NMR – mouse 
[[1jfx]] – Lys – ''Streptomyces coelicolor'' 
[[1gd6]] – Lys – ''Bombyx mori'' 
[[1jug]] – Lys – Echidna 
[[1dkj]] – BqLys – Bobwhite quail 
[[2ihl]] – Lys – Japanese quail 
[[1gbs]] – BsLys – Black swan 
[[1lmn]] – RtLys – Rainbow trout 
[[2eql]] – Lys – horse 
[[1ghl]] – phLys – pheasant 
[[1hhl]] – GfLys – Guinea fowl 
[[1lhm]] – Lys (mutant) – yeast 

===Lys small molecules complexes===

[[3fe0]], [[2d4i]], [[2d4j]], [[1v7s]] - HEWL+ D2O 
[[3m3u]] – HEWL Trp fluorescence 
[[2xjw]] - HEWL + CO 
[[1hf4]], [[1lks]] – HEWL + NO3 
[[3a34]], [[3ems]] - HEWL + arginine 
[[2xth]] – cLys + inhibitor K2PtBr6 
[[3a90]], [[3a91]], [[3a92]], [[3a93]], [[3a94]], [[3a95]], [[3a96]], [[3kam]], [[2pc2]], [[2bpu]], [[1t3p]], [[1h87]] – HEWL + rare earth 
[[2d6b]], [[2hg0]], [[1vat]], [[1gwd]], [[1b2k]], [[1lkr]], [[1azf]], [[8lyz]]- HEWL+ halogen 
[[1vat]] - HEWL + Xe 
[[1n4f]] - HEWL + As 
[[2i6z]] - HEWL + Pt drug 
[[2zyp]] - HEWL + poly (allyl amine) 
[[2f30]], [[2f4a]] – HEWL + urea derivative 
[[2f4g]], [[1ykx]], [[1yky]], [[1ykz]], [[1yl0]], [[1yl1]], [[1z55]] - HEWL + alcohol 
[[1dpw]] – HEWL + MPD 
[[1lcn]] – HEWL + SCN 
[[2zxs]] - HEWL with glycine-amide 
[[2h9j]], [[2h9k]], [[1yik]], [[1yil]] - HEWL + cyclam derivative 
[[1b0d]] – HEWL + p-toluene-sulfonate 
[[2q0m]] - HEWL + tricarbonylmanganese 
[[2war]] – HEWL (mutant) + chitopentaose 
[[2h5z]] – HfLys 1 + chitotetraose – House fly 
[[1hnl]] – hLys + glutathione 
[[1dkk]] – BqLys + NO3 

===Lys complex with glucoside===

[[3a3q]] – HEWL (mutant) + NAG 
[[1sf4]], [[1sf6]], [[1sf7]], [[1sfb]], [[1sfg]], [[1ja2]], [[1ja4]], [[1ja6]], [[1ja7]] – HEWL + NAG oligosaccharide – Powder diffraction 
[[1ubz]], [[1d6p]], [[1d6q]], [[1bb5]] – hLys (mutant) + glycoside 
[[1uc0]], [[1re2]], [[1rem]], [[1rey]], [[1rez]], [[1lzr]], [[1lzs]] - hLys + glycoside 
[[1ljn]], [[1jef]], [[1lzy]] – tuLys + glycoside 
[[1h6m]], [[1at5]], [[1at6]], [[1lzb]], [[1lzc]], [[1lzd]], [[1lze]], [[1lzg]], [[1hew ]]– HEWL + glycoside 
[[1lsy]], [[1lsz]] - HEWL (mutant) + glycoside 
[[1bb6]], [[1bb7]] – RtLys + glycoside 
[[1lmc]] – RtLys + bulgecin 
[[1lmo]], [[1lmp]], [[1lmq]] – RtLys + glucoside 
[[1lsp]] – BsLys + bulgecin 
[[153l]], [[154l]] – Lys +glucoside – goose 

===Phage Lys===

[[2oe4]], [[2oe7]], [[2oe9]], [[2oea]], [[1swz]], [[1cx6]], [[1qtc]], [[1qtd]], [[1qth]], [[1qsb]], [[1qs5]], [[1qs9]], [[1qtb]], [[256l]], [[206l]], [[167l]], [[168l]], [[169l]], [[170l]], [[171l]], [[172l]], [[173l]], [[174l]], [[175l]], [[176l]], [[177l]], [[178l]], [[181l]], [[182l]], [[183l]], [[184l]], [[185l]], [[186l]], [[187l]], [[188l]], [[1nhb]], [[137l]], [[216l]], [[152l]], [[149l]], [[150l]], [[151l]], [[1lyd]], [[2lzm]] - T4Lys – Enterobacteria phage T4 
[[138l]] – T4Lys cross-linked 
[[4lzm]], [[5lzm]], [[6lzm]], [[7lzm]] – T4Lys ionic strength 
[[3l2x]], [[3k2r]], [[3g3v]], [[3g3w]], [[3g3x]], [[2q9d]], [[2q9e]], [[2igc]], [[2ntg]], [[2nth]], [[2ou8]], [[2ou9]], [[1zur]], [[1zwn]], [[1zyt]], [[2cuu]], [[2a4t]] – T4Lys (mutant) spin labeled 
[[3l64]], [[3hwl]], [[3jr6]], [[3gui]], [[3c7w]], [[3c7y]], [[3c7z]], [[3c80]], [[3c81]], [[3c82]], [[3c83]], [[3c8q]], [[3c8r]], [[3c8s]], [[3cdo]], [[3cdq]], [[3cdr]], [[3cdt]], [[3cdv]], [[3f8v]], [[3f9l]], [[3fa0]], [[3fad]], [[3fi5]], [[3dke]], [[3dmv]], [[2o4w]], [[2o79]], [[2o7a]], [[2huk]], [[2hul]], [[2hum]], [[2b7x]], [[2b6t]], [[2b6w]], [[2b6x]], [[2b6y]], [[2b6z]], [[2b70]], [[2b72]], [[2b73]], [[2b74]], [[2b75]], [[1sx7]], [[1swy]], [[1sx2]], [[1t6h]], [[1ssw]], [[1ssy]], [[1t8f]], [[1t8g]], [[1t8a]], [[1t97]], [[1p56]], [[1p5c]], [[1p2l]], [[1p2r]], [[1p36]], [[1p37]], [[1p3n]], [[1p46]], [[1p64]], [[1p6y]], [[1p7s]], [[1pqd]], [[1pqi]], [[1pqj]], [[1pqk]], [[1pqm]], [[1pqo]], [[1oyu]], [[1ks3]], [[1kw5]], [[1kw7]], [[1ky0]], [[1ky1]], [[1l0j]], [[1l0k]], [[1lw9]], [[1lwg]], [[1lwk]], [[1lpy]], [[1llh]], [[1lgu]], [[1li6]], [[1jtm]], [[1jtn]], [[1jqu]], [[1kni]], [[1g06]], [[1g07]], [[1g0g]], [[1g0j]], [[1g0k]], [[1g0l]], [[1g0m]], [[1g0p]], [[1g0q]], [[1g1v]], [[1g1w]], [[1i6s]], [[257l]], [[258l]], [[260l]], [[1epy]], [[1b6i]], [[1cu6]], [[1d9w]], [[1ctw]], [[1cu0]], [[1cu2]], [[1cu3]], [[1cu5]], [[1cv1]], [[1cv4]], [[1cv5]], [[1cv6]], [[1cvk]], [[1cx7]], [[1d2w]], [[1d2y]], [[1d3f]], [[1d3j]], [[1d3m]], [[1d3n]], [[1cv3]], [[1qt3]], [[1qt4]], [[1qt5]], [[1qt6]], [[1qt7]], [[1qt8]], [[1qtv]], [[1qtz]], [[1qud]], [[1qug]], [[1quh]], [[1quo]], [[1qsq]], [[261l]], [[262l]], [[259l]], [[220l]], [[222l]], [[223l]], [[225l]], [[226l]], [[227l]], [[228l]], [[229l]], [[235l]], [[236l]], [[237l]], [[238l]], [[239l]], [[240l]], [[241l]], [[242l]], [[243l]], [[244l]], [[245l]], [[246l]], [[247l]], [[248l]], [[249l]], [[250l]], [[251l]], [[252l]], [[253l]], [[254l]], [[255l]], [[230l]], [[231l]], [[232l]], [[233l]], [[234l]], [[209l]], [[210l]], [[211l]], [[212l]], [[213l]], [[214l]], [[215l]], [[218l]], [[219l]], [[180l]], [[195l]], [[196l]], [[197l]], [[198l]], [[199l]], [[200l]], [[190l]], [[191l]], [[192l]], [[189l]], [[155l]], [[156l]], [[157l]], [[158l]], [[159l]], [[160l]], [[161l]], [[162l]], [[163l]], [[164l]], [[165l]], [[166l]], [[129l]], [[130l]], [[131l]], [[140l]], [[141l]], [[142l]], [[143l]], [[144l]], [[145l]], [[146l]], [[147l]], [[201l]], [[205l]], [[221l]], [[224l]], [[102l]], [[103l]], [[104l]], [[107l]], [[108l]], [[109l]], [[110l]], [[111l]], [[112l]], [[113l]], [[114l]], [[115l]], [[118l]], [[119l]], [[120l]], [[122l]], [[123l]], [[125l]], [[126l]], [[127l]], [[128l]], [[1dya]], [[1dyb]], [[1dyc]], [[1dyd]], [[1dye]], [[1dyf]], [[1dyg]], [[1l00]], [[1l85]], [[1l86]], [[1l87]], [[1l88]], [[1l89]], [[1l90]], [[1l91]], [[1l92]], [[1l93]], [[1l94]], [[1l95]], [[1l96]], [[1l97]], [[1l98]], [[1l99]], [[1lye]], [[1lyf]], [[1lyg]], [[1lyh]], [[1lyi]], [[1lyj]], [[217l]], [[1tla]], [[1l77]], [[1l79]], [[1l80]], [[1l81]], [[1l82]], [[2l78]], [[1l36]], [[1l37]], [[1l38]], [[1l39]], [[1l40]], [[1l41]], [[1l42]], [[1l43]], [[1l44]], [[1l45]], [[1l46]], [[1l47]], [[1l48]], [[1l49]], [[1l50]], [[1l51]], [[1l52]], [[1l53]], [[1l54]], [[1l55]], [[1l56]], [[1l57]], [[1l58]], [[1l59]], [[1l60]], [[1l61]], [[1l62]], [[1l63]], [[1l64]], [[1l65]], [[1l66]], [[1l67]], [[1l68]], [[1l69]], [[1l70]], [[1l71]], [[1l72]], [[1l73]], [[1l74]], [[1l75]], [[1l76]], [[1l17]], [[1l18]], [[1l19]], [[1l20]], [[1l21]], [[1l22]], [[1l23]], [[1l24]], [[1l25]], [[1l26]], [[1l27]], [[1l28]], [[1l29]], [[1l30]], [[1l31]], [[1l32]], [[1l33]], [[1l34]], [[1l35]], [[3lzm]], [[1l01]], [[1l02]], [[1l03]], [[1l04]], [[1l05]], [[1l06]], [[1l07]], [[1l08]], [[1l09]], [[1l10]], [[1l11]], [[1l12]], [[1l13]], [[1l14]], [[1l15]], [[1l16]] – T4Lys (mutant) 
[[1c60]], [[1c61]], [[1c62]], [[1c63]], [[1c64]], [[1c65]], [[1c66]], [[1c67]], [[1c68]], [[1c69]], [[1c6a]], [[1c6b]], [[1c6c]], [[1c6d]], [[1c6e]], [[1c6f]], [[1c6g]], [[1c6h]], [[1c6i]], [[1c6j]], [[1c6k]], [[1c6l]], [[1c6m]], [[1c6n]], [[1c6p]], [[1c6q]], [[1c6t]] - T4Lys (mutant) + noble gas 
[[3ht6]], [[3ht7]], [[3ht8]], [[3ht9]], [[3htb]], [[3hu8]], [[3huq]], [[3guj]], [[3guk]], [[3gul]], [[3gum]], [[3gun]], [[3guo]], [[3gup]], [[3dmx]], [[3dmz]], [[3dn0]], [[3dn1]], [[3dn2]], [[3dn3]], [[3dn4]], [[3dn6]], [[3dn8]], [[3dna]], [[2rb1]], [[2ray]], [[2raz]], [[2rb0]], [[2rb2]], [[2rbn]], [[2rbo]], [[2rbq]], [[2rbr]], [[2rbs]], [[2oty]],[[2otz]], [[1owy]], [[1owz]], [[1ov5]], [[1ov7]], [[1ovh]], [[1ovj]], [[1ovk]], [[1lgw]], [[1lgx]], [[1li2]], [[1li3]], [[1l83]], [[1l84]] – T4Lys (mutant) + benzene derivative 
[[3htd]], [[3htf]], [[3htg]], [[3hu9]], [[3hua]], [[3huk]], [[3hh3]], [[3hh4]], [[3hh5]], [[3hh6]], [[2rbp]], [[2ou0]], [[2f2q]], [[2f32]], [[2f47]], [[1xep]] – T4Lys (mutant) + inhibitor 
[[148l]] - T4Lys (mutant) + glucoside 
[[3d3d]], [[1d9u]] – lamLys + chitohexasaccharide 
[[1am7]] – lamLys - Enterobacteria phage λ 
[[2anv]], [[2anx]] – Lys (mutant)]] - Enterobacteria phage p22 
[[1xjt]], [[1xju]] - Lys - Enterobacteria phage p1 
[[1lba]] - T7Lys - Enterobacteria phage T7 

===Lys protein complex===

[[3m18]], [[3g3a]], [[3g3b]] - HEWL + Variable lymphocyte receptor – Marine lamprey 
[[3a67]], [[3a6b]], [[3a6c]], [[2yss]], [[2eiz]], [[2dqc]], [[2dqd]], [[2dqe]], [[2dqf]], [[2dqg]], [[2dqh]], [[2dqi]], [[2dqj]], [[1j1o]], [[1j1p]], [[1j1x]], [[1ic4]], [[1ic5]], [[1ic7]] – HEWL + mLys antibody HYHEL-10 (mutant) 
[[1xgp]], [[1xgq]], [[1xgr]], [[1xgt]], [[1xgu]] – HEWL + mLys antibody HYHEL-63 
[[3d9a]], [[2eks]], [[1ua6]], [[1c08]], [[3hfm]] – HEWL + mLys antibody HYHEL-10 
[[1uac]] - tuLys C + mLys antibody HYHEL-10 
[[1yqv]], [[2iff]] – HEWL + mLys antibody HYHEL-5 
[[1bql]] – BqLys + mLys antibody HYHEL-5 
[[1ndg]] – HEWL + mLys antibody HYHEL-8 
[[1ndm]] – HEWL + mLys antibody HYHEL-26 
[[1dqj]] - HEWL + mLys antibody HYHEL-63 
[[1nby]], [[1nbz]] – HEWL (mutant) + mLys antibody HYHEL-63 
[[1g7h]], [[1g7i]], [[1g7j]], [[1g7l]], [[1g7m]], [[1kip]], [[1kiq]], [[1kir]] – HEWL + mAnti-HEWL monoclonal antibody (mutant) 
[[1mlc]], [[1vfb]] - HEWL + mIGG1-κ D44.1 FAB 
[[1a2y]] - HEWL (mutant) + mIGG1-κ D1.3 FV 
[[1fdl]] - HEWL + mIGG1-κ D1.3 FAB 
[[1jhl]] – phLys + mIGG1-κ D11.15 FV 
[[1fbi]] – GfLys + mIGG1 F9.13.7 FAB 
[[2znw]], [[2znx]] – HEWL + hSCFV10 antibody 
[[1bvk]] - HEWL + hAnti Lys FV antibody 
[[1dzb]] – tuLys + mSCFV 1F9 
[[1zv5]], [[1zvh]], [[1zvy]], [[1zmy]], [[1ri8]], [[1rjc]], [[1xfp]], [[1jtp]], [[1jtt]], [[1jto]], [[1mel]] - HEWL + cAntibody heavy chain domain – camel 
[[1op9]] - hLys C + cAntibody heavy chain domain 
[[3otp]] – HEWL + EcProtease DO – ''Escherichia coli'' 
[[3f6z]] - HEWL + MLIC – ''Pseudomonas aeruginosa'' 
[[3eba]] – hLys C + hCABHUL6 
[[2qb0]], [[2qar]] – T4Lys/E80 TELSAM domain 
[[2i25]], [[2i26]] - HEWL +NsAntigen receptor PBLA8 variable domain – Nurse shark 
[[1sq2]], [[1t6v]] – HEWL +NsNew Antigen receptor variable domain 
[[1gpq]] – HEWL + EcInhibitor of Vertebrate Lys 
[[1aro]] – T7Lys + T7 RNA polymerase 

===Some Useful External Links===
[http://en.wikipedia.org/wiki/Lysozyme Lysozyme]

[http://en.wikipedia.org/wiki/Glycoside_hydrolase#Retaining_glycoside_hydrolases Retaining Glycoside Hydrolases]

===References===
<references/>

Hen Egg-White (HEW) Lysozyme

2011-03-31T01:07:05Z

Anne Goodling:

<applet load='aln_1H6M_to_1HEW_2.pdb' size='300' frame='true' align='right' caption=' Hen Egg White (HEW) Lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to the active site, PDBid 1HEW' scene='User:Judy_Voet/Lysozyme/Lysozyme1/16' />
Lysozyme was the first enzyme whose X-ray structure was determined <ref> PMID 5840126</ref><ref>Phillips, D. C. The hen egg white lysozyme molecule. Proc. Natl Acad. Sci. USA 57, 483-495 (1967)</ref>. This <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>scene </scene> shows Hen Egg White (HEW) lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to a cleft in the enzyme. David Phillips, who determined the structure in 1965, saw that the cleft was large enough to fit three more saccharide units. He therefore built a model extending the trisaccharide to a
<scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> that fits into the cleft, labeling the sugar subsites A-F<ref> coordinates of the model kindly provided by Louise Johnson</ref>. Alternately click on <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>trisaccharide</scene> and <scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> to turn the modeled portion of the hexasaccharide on and off.
The interesting thing about the model was that the only way that the hexasaccharide would fit into the cleft was if the 4th saccharide (in subsite D) was strained into a <scene name='User:Judy_Voet/Lysozyme/Half-chair/2'>half-chair conformation</scene>. This conformation is what would be necessary for the formation of an oxocarbenium ion (oxionium ion). When the model was studied, <scene name='User:Judy_Voet/Lysozyme/Glu_35/1'>Glu 35</scene> was found to be in an ideal location to act as a general acid catalyst, 3.34 Angstroms from the bridging oxygen between the 4th and 5th saccharide units. <scene name='User:Judy_Voet/Lysozyme/Asp_52/2'>Asp 52</scene> appeared to be too far away (2.69 angstroms) in the static lysozyme structure to have formed a covalent bond with C1 of the half-chair model in the D site, and no covalent intermediate had ever been detected, so Phillips proposed that it acted as an electrostatic stabilizer of the oxonium ion (referred to as The Phillips Mechanism).

Then, in 2001, Stephen Withers published <scene name='User:Judy_Voet/Lysozyme/1h6m/3'>1H6M</scene>,<ref>PMID 11518970</ref> in which Glu 35 had been mutated to Gln to remove the general acid catalyst. The substrate contained NAG-2-fluoro-glucosyl fluoride (NAG2FGlcF). The fluoro group on C-1 does not require acid catalysis to be a good leaving group, and the remaining saccharide, in the absence of the acid necessary to catalyse the second step of the reaction, was demonstrated to form a <scene name='User:Judy_Voet/Lysozyme/Covalent/1'> covalent intermediate</scene>. In this <scene name='User:Judy_Voet/Lysozyme/Superposition/2'>superposition</scene> of the half chair model with 1HEW (greens) and the covalent intermediate in 1H6M (blues), note the relatively small motions of Asp 52 and C1 of the sugar ring in going from the model to the covalent intermediate. to observe the motion from the <scene name='User:Judy_Voet/Lysozyme/Asp52_halfchair/1'>half-chair</scene> to the <scene name='User:Judy_Voet/Lysozyme/Covalent/2'>covalent intermediate</scene> just toggle between the two green links.
<applet load='aln_1H6M_to_1HEW_2.pdb' size='300' frame='true' align='right' caption='NAG-2-deoxy-2-fluoro-glucosyl fluoride (NAG2FGlcF) bound to Glu35Gln HEW Lysozyme PDBid 1H6M' scene='User:Judy_Voet/Lysozyme/1h6m/3'/>

== 3D Structures of Lysozyme ==

===Lys===

[[2x0a]], [[3iju]], [[3ijv]], [[3a8z]], [[2w1y]], [[2w1m]], [[2w1x]], [[2w1l]], [[3e3d]], [[3exd]], [[2zq3]], [[2zq4]], [[3b72]], [[3b6l]], [[2z12]], [[2z18]], [[2z19]], [[2vb1]], [[2hu3]], [[2hub]], [[2htx]], [[2hu1]], [[2yvb]], [[2epe]], [[2g4p]], [[2g4q]], [[2cgi]], [[2b5z]], [[2d4k]], [[2d91]], [[2f2n]], [[2fbb]], [[2c8o]], [[2c8p]], [[2a6u]], [[2aub]], [[2blx]], [[2bly]], [[2a7d]], [[2a7f]], [[1wtm]], [[1wtn]], [[1w6z]], [[1vdp]], [[1vdq]], [[1vds]], [[1vdt]], [[1ved]], [[1v7t]], [[1ps5]], [[2cds]], [[1lj3]], [[1lj4]], [[1lje]], [[1ljf]], [[1ljg]], [[1ljh]], [[1lji]], [[1ljj]], [[1ljk]], [[1jis]], [[1jit]], [[1jiy]], [[1jj0]], [[1jj1]], [[1jj3]], [[1iee]], [[1qio]], [[1f0w]], [[1f10]], [[1dpx]], [[1c10]], [[1qtk]], [[1lz8]], [[1lz9]], [[1bhz]], [[1bgi]], [[1bwh]], [[1bwi]], [[1bwj]], [[1bvx]], [[1hsw]], [[1hsx]], [[1lpi]], [[4lzt]], [[3lzt]], [[1aki]], [[1jpo]], [[1rfp]], [[193l]], [[194l]], [[5lym]], [[1lza]], [[3lyt]], [[4lyt]], [[5lyt]], [[6lyt]], [[2lzt]], [[1lzt]], [[1lzh]], [[2lzh]], [[7lyz]], [[1lyz]], [[2lyz]], [[3lyz]], [[4lyz]], [[5lyz]], [[6lyz]] - HEWL – chicken 
[[1xei]], [[1xej]], [[1xek]], [[1uco]], [[1lma]], [[4lym]] – HEWL low hydration 
[[1lsa]], [[1lsb]], [[1lsc]], [[1lsd]], [[1lse]], [[1lsf]], [[1lys]] – HEWL temperature influence 
[[2lym]], [[3lym]] – HEWL pressure influence 
[[132l]] – HEWL methylated 
[[1rcm]] – HEWL 3 S-S form 
[[2xbr]], [[2xbs]]- HEWL– Raman crystallography 
[[2zwb]], [[1io5]], [[1lzn]] - HEWL– Neutron 
[[1gxv]], [[1gxx]], [[1e8l]] - HEWL- NMR 
[[2hs7]], [[2hso]], [[2hs9]]- HEWL– Powder diffraction 
[[1ir7]], [[1ir8]], [[1ir9]], [[1ioq]], [[1ior]], [[1ios]], [[1iot]], [[1flq]], [[1flu]], [[1flw]], [[1fly]], [[1fn5]], [[1kxw]], [[1kxx]], [[1kxy]], [[1uia]], [[1uib]], [[1uic]], [[1uid]], [[1uie]], [[1uif]], [[1uig]], [[1uih]], [[1lsm]], [[1lsn]], [[1hel]], [[1hem]], [[1hen]], [[1heo]], [[1hep]], [[1heq]], [[1her]] – HEWL (mutant) 
[[1lyo]], [[2lyo]], [[3lyo]], [[4lyo]] – HEWL cross-linked 
[[1xft]] - tuLys – turkey - Powder diffraction 
[[1jse]], [[1tew]], [[135l]], [[2lz2]], [[1lz2]] – tuLys 
[[3lz2]] – tuLys - Laue 
[[3ab6]] – Lys + NAG3 – Hard clam 
[[2x8r]] – Lys GH25 – ''Aspergillus fumigatus'' 
[[3mgw]] – Lys G – Atlantic salmon 
[[3gxk]], [[3gxr]] – Lys G + NAG – Atlantic cod 
[[2fbd]] – HfLys 1 
[[3cb7]] – HfLys 2 
[[2zij]], [[2zik]], [[2zil]], [[2nwd]], [[1iwt]], [[1iwu]], [[1iwv]], [[1iww]], [[1iwx]], [[1iwy]], [[1iwz]], [[1jwr]], [[1jsf]], [[1rex]], [[1lz1]] – hLys – human 
[[1w08]], [[1ix0]], [[1ioc]], [[1ip1]], [[1ip2]], [[1ip3]], [[1ip4]], [[1ip5]], [[1ip6]], [[1ip7]], [[1qsw]], [[1gev]], [[1gez]], [[1gf0]], [[1gf3]], [[1gf4]], [[1gf5]], [[1gf6]], [[1gf7]], [[1i1z]], [[1i20]], [[1i22]], [[1gfr]], [[1gft]], [[1gfu]], [[1gfv]], [[1gf8]], [[1gf9]], [[1gfa]], [[1gfe]], [[1gfg]], [[1gfh]], [[1gfj]], [[1gfk]], [[1inu]], [[1gdx]], [[1ge0]], [[1ge1]], [[1ge2]], [[1ge3]], [[1ge4]], [[1gdw]], [[1gaz]], [[1gb0]], [[1gb2]], [[1gb3]], [[1gb5]], [[1gb6]], [[1gb7]], [[1gb8]], [[1gb9]], [[1gbo]], [[1gbw]], [[1gbx]], [[1gby]], [[1gbz]], [[1gay]], [[1eq4]], [[1eq5]], [[1eqe]], [[1c7p]], [[1di3]], [[1di4]], [[1di5]], [[1c43]], [[1c45]], [[1c46]], [[1ckg]], [[1cj6]], [[1cj7]], [[1cj8]], [[1cj9]], [[1ckc]], [[1ckd]], [[1ckf]], [[1ckh]], [[1b5z]], [[1b70]], [[1b7q]], [[1b7r]], [[1b7s]], [[1b7l]], [[1b7m]], [[1b7n]], [[1b7p]], [[1b5u]], [[1b5v]], [[1b5w]], [[1b5x]], [[1b5y]], [[1bb3]], [[1bb4]], [[2bqa]], [[2bqb]], [[2bqc]], [[2bqd]], [[2bqe]], [[2bqf]], [[2bqg]], [[2bqh]], [[2bqi]], [[2bqj]], [[2bqk]], [[2bql]], [[2bqm]], [[2bqn]], [[2bqo]], [[2mea]], [[2meb]], [[2mec]], [[2med]], [[2mee]], [[2mef]], [[2meg]], [[2meh]], [[2mei]], [[1wqm]], [[1wqn]], [[1wqo]], [[1wqp]], [[1wqq]], [[1wqr]], [[2heb]], [[2hea]], [[2hec]], [[2hed]], [[2hee]], [[2hef]], [[1jka]], [[1jkb]], [[1jkc]], [[1jkd]], [[1loz]], [[1lyy]], [[1oua]], [[1oub]], [[1ouc]], [[1oud]], [[1oue]], [[1ouf]], [[1oug]], [[1ouh]], [[1oui]], [[1ouj]], [[207l]], [[208l ]], [[1yam]], [[1yan]], [[1yao]], [[1yap]], [[1yaq]], [[1lmt]], [[1lhh]], [[1lhi]], [[1lhj]], [[1lhk]], [[1lhl]], [[133l]], [[134l]], [[1lz4]], [[1lz5]], [[1lz6]], [[1laa]], [[1tay]], [[1tby]], [[1tcy]], [[1tdy]], [[2lhm]], [[3lhm]] – hLys (mutant) 
[[1iy3]], [[1iy4]] – hLys - NMR 
[[2z2f]] – Lys – Bovine 
[[2cwi]], [[1el1]], [[1qqy]] – dLys - dog 
[[2z2e]] – dLys (mutant) 
[[1i56]] – dLys – NMR 
[[2dqa]] – Lys – ''Tapes japonica'' 
[[2gv0]] – Lys – Soft-shelled turtle 
[[1ivm]] – mLys M – NMR – mouse 
[[1jfx]] – Lys – ''Streptomyces coelicolor'' 
[[1gd6]] – Lys – ''Bombyx mori'' 
[[1jug]] – Lys – Echidna 
[[1dkj]] – BqLys – Bobwhite quail 
[[2ihl]] – Lys – Japanese quail 
[[1gbs]] – BsLys – Black swan 
[[1lmn]] – RtLys – Rainbow trout 
[[2eql]] – Lys – horse 
[[1ghl]] – phLys – pheasant 
[[1hhl]] – GfLys – Guinea fowl 
[[1lhm]] – Lys (mutant) – yeast 

===Lys small molecules complexes===

[[3fe0]], [[2d4i]], [[2d4j]], [[1v7s]] - HEWL+ D2O 
[[3m3u]] – HEWL Trp fluorescence 
[[2xjw]] - HEWL + CO 
[[1hf4]], [[1lks]] – HEWL + NO3 
[[3a34]], [[3ems]] - HEWL + arginine 
[[2xth]] – cLys + inhibitor K2PtBr6 
[[3a90]], [[3a91]], [[3a92]], [[3a93]], [[3a94]], [[3a95]], [[3a96]], [[3kam]], [[2pc2]], [[2bpu]], [[1t3p]], [[1h87]] – HEWL + rare earth 
[[2d6b]], [[2hg0]], [[1vat]], [[1gwd]], [[1b2k]], [[1lkr]], [[1azf]], [[8lyz]]- HEWL+ halogen 
[[1vat]] - HEWL + Xe 
[[1n4f]] - HEWL + As 
[[2i6z]] - HEWL + Pt drug 
[[2zyp]] - HEWL + poly (allyl amine) 
[[2f30]], [[2f4a]] – HEWL + urea derivative 
[[2f4g]], [[1ykx]], [[1yky]], [[1ykz]], [[1yl0]], [[1yl1]], [[1z55]] - HEWL + alcohol 
[[1dpw]] – HEWL + MPD 
[[1lcn]] – HEWL + SCN 
[[2zxs]] - HEWL with glycine-amide 
[[2h9j]], [[2h9k]], [[1yik]], [[1yil]] - HEWL + cyclam derivative 
[[1b0d]] – HEWL + p-toluene-sulfonate 
[[2q0m]] - HEWL + tricarbonylmanganese 
[[2war]] – HEWL (mutant) + chitopentaose 
[[2h5z]] – HfLys 1 + chitotetraose – House fly 
[[1hnl]] – hLys + glutathione 
[[1dkk]] – BqLys + NO3 

===Lys complex with glucoside===

[[3a3q]] – HEWL (mutant) + NAG 
[[1sf4]], [[1sf6]], [[1sf7]], [[1sfb]], [[1sfg]], [[1ja2]], [[1ja4]], [[1ja6]], [[1ja7]] – HEWL + NAG oligosaccharide – Powder diffraction 
[[1ubz]], [[1d6p]], [[1d6q]], [[1bb5]] – hLys (mutant) + glycoside 
[[1uc0]], [[1re2]], [[1rem]], [[1rey]], [[1rez]], [[1lzr]], [[1lzs]] - hLys + glycoside 
[[1ljn]], [[1jef]], [[1lzy]] – tuLys + glycoside 
[[1h6m]], [[1at5]], [[1at6]], [[1lzb]], [[1lzc]], [[1lzd]], [[1lze]], [[1lzg]], [[1hew ]]– HEWL + glycoside 
[[1lsy]], [[1lsz]] - HEWL (mutant) + glycoside 
[[1bb6]], [[1bb7]] – RtLys + glycoside 
[[1lmc]] – RtLys + bulgecin 
[[1lmo]], [[1lmp]], [[1lmq]] – RtLys + glucoside 
[[1lsp]] – BsLys + bulgecin 
[[153l]], [[154l]] – Lys +glucoside – goose 

===Phage Lys===

[[2oe4]], [[2oe7]], [[2oe9]], [[2oea]], [[1swz]], [[1cx6]], [[1qtc]], [[1qtd]], [[1qth]], [[1qsb]], [[1qs5]], [[1qs9]], [[1qtb]], [[256l]], [[206l]], [[167l]], [[168l]], [[169l]], [[170l]], [[171l]], [[172l]], [[173l]], [[174l]], [[175l]], [[176l]], [[177l]], [[178l]], [[181l]], [[182l]], [[183l]], [[184l]], [[185l]], [[186l]], [[187l]], [[188l]], [[1nhb]], [[137l]], [[216l]], [[152l]], [[149l]], [[150l]], [[151l]], [[1lyd]], [[2lzm]] - T4Lys – Enterobacteria phage T4 
[[138l]] – T4Lys cross-linked 
[[4lzm]], [[5lzm]], [[6lzm]], [[7lzm]] – T4Lys ionic strength 
[[3l2x]], [[3k2r]], [[3g3v]], [[3g3w]], [[3g3x]], [[2q9d]], [[2q9e]], [[2igc]], [[2ntg]], [[2nth]], [[2ou8]], [[2ou9]], [[1zur]], [[1zwn]], [[1zyt]], [[2cuu]], [[2a4t]] – T4Lys (mutant) spin labeled 
[[3l64]], [[3hwl]], [[3jr6]], [[3gui]], [[3c7w]], [[3c7y]], [[3c7z]], [[3c80]], [[3c81]], [[3c82]], [[3c83]], [[3c8q]], [[3c8r]], [[3c8s]], [[3cdo]], [[3cdq]], [[3cdr]], [[3cdt]], [[3cdv]], [[3f8v]], [[3f9l]], [[3fa0]], [[3fad]], [[3fi5]], [[3dke]], [[3dmv]], [[2o4w]], [[2o79]], [[2o7a]], [[2huk]], [[2hul]], [[2hum]], [[2b7x]], [[2b6t]], [[2b6w]], [[2b6x]], [[2b6y]], [[2b6z]], [[2b70]], [[2b72]], [[2b73]], [[2b74]], [[2b75]], [[1sx7]], [[1swy]], [[1sx2]], [[1t6h]], [[1ssw]], [[1ssy]], [[1t8f]], [[1t8g]], [[1t8a]], [[1t97]], [[1p56]], [[1p5c]], [[1p2l]], [[1p2r]], [[1p36]], [[1p37]], [[1p3n]], [[1p46]], [[1p64]], [[1p6y]], [[1p7s]], [[1pqd]], [[1pqi]], [[1pqj]], [[1pqk]], [[1pqm]], [[1pqo]], [[1oyu]], [[1ks3]], [[1kw5]], [[1kw7]], [[1ky0]], [[1ky1]], [[1l0j]], [[1l0k]], [[1lw9]], [[1lwg]], [[1lwk]], [[1lpy]], [[1llh]], [[1lgu]], [[1li6]], [[1jtm]], [[1jtn]], [[1jqu]], [[1kni]], [[1g06]], [[1g07]], [[1g0g]], [[1g0j]], [[1g0k]], [[1g0l]], [[1g0m]], [[1g0p]], [[1g0q]], [[1g1v]], [[1g1w]], [[1i6s]], [[257l]], [[258l]], [[260l]], [[1epy]], [[1b6i]], [[1cu6]], [[1d9w]], [[1ctw]], [[1cu0]], [[1cu2]], [[1cu3]], [[1cu5]], [[1cv1]], [[1cv4]], [[1cv5]], [[1cv6]], [[1cvk]], [[1cx7]], [[1d2w]], [[1d2y]], [[1d3f]], [[1d3j]], [[1d3m]], [[1d3n]], [[1cv3]], [[1qt3]], [[1qt4]], [[1qt5]], [[1qt6]], [[1qt7]], [[1qt8]], [[1qtv]], [[1qtz]], [[1qud]], [[1qug]], [[1quh]], [[1quo]], [[1qsq]], [[261l]], [[262l]], [[259l]], [[220l]], [[222l]], [[223l]], [[225l]], [[226l]], [[227l]], [[228l]], [[229l]], [[235l]], [[236l]], [[237l]], [[238l]], [[239l]], [[240l]], [[241l]], [[242l]], [[243l]], [[244l]], [[245l]], [[246l]], [[247l]], [[248l]], [[249l]], [[250l]], [[251l]], [[252l]], [[253l]], [[254l]], [[255l]], [[230l]], [[231l]], [[232l]], [[233l]], [[234l]], [[209l]], [[210l]], [[211l]], [[212l]], [[213l]], [[214l]], [[215l]], [[218l]], [[219l]], [[180l]], [[195l]], [[196l]], [[197l]], [[198l]], [[199l]], [[200l]], [[190l]], [[191l]], [[192l]], [[189l]], [[155l]], [[156l]], [[157l]], [[158l]], [[159l]], [[160l]], [[161l]], [[162l]], [[163l]], [[164l]], [[165l]], [[166l]], [[129l]], [[130l]], [[131l]], [[140l]], [[141l]], [[142l]], [[143l]], [[144l]], [[145l]], [[146l]], [[147l]], [[201l]], [[205l]], [[221l]], [[224l]], [[102l]], [[103l]], [[104l]], [[107l]], [[108l]], [[109l]], [[110l]], [[111l]], [[112l]], [[113l]], [[114l]], [[115l]], [[118l]], [[119l]], [[120l]], [[122l]], [[123l]], [[125l]], [[126l]], [[127l]], [[128l]], [[1dya]], [[1dyb]], [[1dyc]], [[1dyd]], [[1dye]], [[1dyf]], [[1dyg]], [[1l00]], [[1l85]], [[1l86]], [[1l87]], [[1l88]], [[1l89]], [[1l90]], [[1l91]], [[1l92]], [[1l93]], [[1l94]], [[1l95]], [[1l96]], [[1l97]], [[1l98]], [[1l99]], [[1lye]], [[1lyf]], [[1lyg]], [[1lyh]], [[1lyi]], [[1lyj]], [[217l]], [[1tla]], [[1l77]], [[1l79]], [[1l80]], [[1l81]], [[1l82]], [[2l78]], [[1l36]], [[1l37]], [[1l38]], [[1l39]], [[1l40]], [[1l41]], [[1l42]], [[1l43]], [[1l44]], [[1l45]], [[1l46]], [[1l47]], [[1l48]], [[1l49]], [[1l50]], [[1l51]], [[1l52]], [[1l53]], [[1l54]], [[1l55]], [[1l56]], [[1l57]], [[1l58]], [[1l59]], [[1l60]], [[1l61]], [[1l62]], [[1l63]], [[1l64]], [[1l65]], [[1l66]], [[1l67]], [[1l68]], [[1l69]], [[1l70]], [[1l71]], [[1l72]], [[1l73]], [[1l74]], [[1l75]], [[1l76]], [[1l17]], [[1l18]], [[1l19]], [[1l20]], [[1l21]], [[1l22]], [[1l23]], [[1l24]], [[1l25]], [[1l26]], [[1l27]], [[1l28]], [[1l29]], [[1l30]], [[1l31]], [[1l32]], [[1l33]], [[1l34]], [[1l35]], [[3lzm]], [[1l01]], [[1l02]], [[1l03]], [[1l04]], [[1l05]], [[1l06]], [[1l07]], [[1l08]], [[1l09]], [[1l10]], [[1l11]], [[1l12]], [[1l13]], [[1l14]], [[1l15]], [[1l16]] – T4Lys (mutant) 
[[1c60]], [[1c61]], [[1c62]], [[1c63]], [[1c64]], [[1c65]], [[1c66]], [[1c67]], [[1c68]], [[1c69]], [[1c6a]], [[1c6b]], [[1c6c]], [[1c6d]], [[1c6e]], [[1c6f]], [[1c6g]], [[1c6h]], [[1c6i]], [[1c6j]], [[1c6k]], [[1c6l]], [[1c6m]], [[1c6n]], [[1c6p]], [[1c6q]], [[1c6t]] - T4Lys (mutant) + noble gas 
[[3ht6]], [[3ht7]], [[3ht8]], [[3ht9]], [[3htb]], [[3hu8]], [[3huq]], [[3guj]], [[3guk]], [[3gul]], [[3gum]], [[3gun]], [[3guo]], [[3gup]], [[3dmx]], [[3dmz]], [[3dn0]], [[3dn1]], [[3dn2]], [[3dn3]], [[3dn4]], [[3dn6]], [[3dn8]], [[3dna]], [[2rb1]], [[2ray]], [[2raz]], [[2rb0]], [[2rb2]], [[2rbn]], [[2rbo]], [[2rbq]], [[2rbr]], [[2rbs]], [[2oty]],[[2otz]], [[1owy]], [[1owz]], [[1ov5]], [[1ov7]], [[1ovh]], [[1ovj]], [[1ovk]], [[1lgw]], [[1lgx]], [[1li2]], [[1li3]], [[1l83]], [[1l84]] – T4Lys (mutant) + benzene derivative 
[[3htd]], [[3htf]], [[3htg]], [[3hu9]], [[3hua]], [[3huk]], [[3hh3]], [[3hh4]], [[3hh5]], [[3hh6]], [[2rbp]], [[2ou0]], [[2f2q]], [[2f32]], [[2f47]], [[1xep]] – T4Lys (mutant) + inhibitor 
[[148l]] - T4Lys (mutant) + glucoside 
[[3d3d]], [[1d9u]] – lamLys + chitohexasaccharide 
[[1am7]] – lamLys - Enterobacteria phage λ 
[[2anv]], [[2anx]] – Lys (mutant)]] - Enterobacteria phage p22 
[[1xjt]], [[1xju]] - Lys - Enterobacteria phage p1 
[[1lba]] - T7Lys - Enterobacteria phage T7 

===Lys protein complex===

[[3m18]], [[3g3a]], [[3g3b]] - HEWL + Variable lymphocyte receptor – Marine lamprey 
[[3a67]], [[3a6b]], [[3a6c]], [[2yss]], [[2eiz]], [[2dqc]], [[2dqd]], [[2dqe]], [[2dqf]], [[2dqg]], [[2dqh]], [[2dqi]], [[2dqj]], [[1j1o]], [[1j1p]], [[1j1x]], [[1ic4]], [[1ic5]], [[1ic7]] – HEWL + mLys antibody HYHEL-10 (mutant) 
[[1xgp]], [[1xgq]], [[1xgr]], [[1xgt]], [[1xgu]] – HEWL + mLys antibody HYHEL-63 
[[3d9a]], [[2eks]], [[1ua6]], [[1c08]], [[3hfm]] – HEWL + mLys antibody HYHEL-10 
[[1uac]] - tuLys C + mLys antibody HYHEL-10 
[[1yqv]], [[2iff]] – HEWL + mLys antibody HYHEL-5 
[[1bql]] – BqLys + mLys antibody HYHEL-5 
[[1ndg]] – HEWL + mLys antibody HYHEL-8 
[[1ndm]] – HEWL + mLys antibody HYHEL-26 
[[1dqj]] - HEWL + mLys antibody HYHEL-63 
[[1nby]], [[1nbz]] – HEWL (mutant) + mLys antibody HYHEL-63 
[[1g7h]], [[1g7i]], [[1g7j]], [[1g7l]], [[1g7m]], [[1kip]], [[1kiq]], [[1kir]] – HEWL + mAnti-HEWL monoclonal antibody (mutant) 
[[1mlc]], [[1vfb]] - HEWL + mIGG1-κ D44.1 FAB 
[[1a2y]] - HEWL (mutant) + mIGG1-κ D1.3 FV 
[[1fdl]] - HEWL + mIGG1-κ D1.3 FAB 
[[1jhl]] – phLys + mIGG1-κ D11.15 FV 
[[1fbi]] – GfLys + mIGG1 F9.13.7 FAB 
[[2znw]], [[2znx]] – HEWL + hSCFV10 antibody 
[[1bvk]] - HEWL + hAnti Lys FV antibody 
[[1dzb]] – tuLys + mSCFV 1F9 
[[1zv5]], [[1zvh]], [[1zvy]], [[1zmy]], [[1ri8]], [[1rjc]], [[1xfp]], [[1jtp]], [[1jtt]], [[1jto]], [[1mel]] - HEWL + cAntibody heavy chain domain – camel 
[[1op9]] - hLys C + cAntibody heavy chain domain 
[[3otp]] – HEWL + EcProtease DO – ''Escherichia coli'' 
[[3f6z]] - HEWL + MLIC – ''Pseudomonas aeruginosa'' 
[[3eba]] – hLys C + hCABHUL6 
[[2qb0]], [[2qar]] – T4Lys/E80 TELSAM domain 
[[2i25]], [[2i26]] - HEWL +NsAntigen receptor PBLA8 variable domain – Nurse shark 
[[1sq2]], [[1t6v]] – HEWL +NsNew Antigen receptor variable domain 
[[1gpq]] – HEWL + EcInhibitor of Vertebrate Lys 
[[1aro]] – T7Lys + T7 RNA polymerase 

===Some Useful External Links===
[http://en.wikipedia.org/wiki/Lysozyme Lysozyme]

[http://en.wikipedia.org/wiki/Glycoside_hydrolase#Retaining_glycoside_hydrolases Retaining Glycoside Hydrolases]

===References===
<references/>

Hen Egg-White (HEW) Lysozyme

2011-03-31T01:06:24Z

Anne Goodling:

<applet load='aln_1H6M_to_1HEW_2.pdb' size='300' frame='true' align='right' caption=' Hen Egg White (HEW) Lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to the active site, PDBid 1HEW' scene='User:Judy_Voet/Lysozyme/Lysozyme1/16' />
Lysozyme was the first enzyme whose X-ray structure was determined <ref> PMID 5840126</ref><ref>Phillips, D. C. The hen egg white lysozyme molecule. Proc. Natl Acad. Sci. USA 57, 483-495 (1967)</ref>. This <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>scene </scene> shows Hen Egg White (HEW) lysozyme containing a trisaccharide of N-acetylglucosamine (NAG) bound to a cleft in the enzyme. David Phillips, who determined the structure in 1965, saw that the cleft was large enough to fit three more saccharide units. He therefore built a model extending the trisaccharide to a
<scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> that fits into the cleft, labeling the sugar subsites A-F<ref> coordinates of the model kindly provided by Louise Johnson</ref>. Alternately click on <scene name='User:Judy_Voet/Lysozyme/Lysozyme1/15'>trisaccharide</scene> and <scene name='User:Judy_Voet/Lysozyme/Lysozyme1_hexamer/7'>hexasaccharide</scene> to turn the modeled portion of the hexasaccharide on and off.
The interesting thing about the model was that the only way that the hexasaccharide would fit into the cleft was if the 4th saccharide (in subsite D) was strained into a <scene name='User:Judy_Voet/Lysozyme/Half-chair/2'>half-chair conformation</scene>. This conformation is what would be necessary for the formation of an oxocarbenium ion (oxionium ion). When the model was studied, <scene name='User:Judy_Voet/Lysozyme/Glu_35/1'>Glu 35</scene> was found to be in an ideal location to act as a general acid catalyst, 3.34 Angstroms from the bridging oxygen between the 4th and 5th saccharide units. <scene name='User:Judy_Voet/Lysozyme/Asp_52/2'>Asp 52</scene> appeared to be too far away (2.69 angstroms) in the static lysozyme structure to have formed a covalent bond with C1 of the half-chair model in the D site, and no covalent intermediate had ever been detected, so Phillips proposed that it acted as an electrostatic stabilizer of the oxonium ion (referred to as The Phillips Mechanism).

<applet load='aln_1H6M_to_1HEW_2.pdb' size='300' frame='true' align='right' caption='NAG-2-deoxy-2-fluoro-glucosyl fluoride (NAG2FGlcF) bound to Glu35Gln HEW Lysozyme PDBid 1H6M' scene='User:Judy_Voet/Lysozyme/1h6m/3'/>
Then, in 2001, Stephen Withers published <scene name='User:Judy_Voet/Lysozyme/1h6m/3'>1H6M</scene>,<ref>PMID 11518970</ref> in which Glu 35 had been mutated to Gln to remove the general acid catalyst. The substrate contained NAG-2-fluoro-glucosyl fluoride (NAG2FGlcF). The fluoro group on C-1 does not require acid catalysis to be a good leaving group, and the remaining saccharide, in the absence of the acid necessary to catalyse the second step of the reaction, was demonstrated to form a <scene name='User:Judy_Voet/Lysozyme/Covalent/1'> covalent intermediate</scene>. In this <scene name='User:Judy_Voet/Lysozyme/Superposition/2'>superposition</scene> of the half chair model with 1HEW (greens) and the covalent intermediate in 1H6M (blues), note the relatively small motions of Asp 52 and C1 of the sugar ring in going from the model to the covalent intermediate. to observe the motion from the <scene name='User:Judy_Voet/Lysozyme/Asp52_halfchair/1'>half-chair</scene> to the <scene name='User:Judy_Voet/Lysozyme/Covalent/2'>covalent intermediate</scene> just toggle between the two green links.

== 3D Structures of Lysozyme ==

===Lys===

[[2x0a]], [[3iju]], [[3ijv]], [[3a8z]], [[2w1y]], [[2w1m]], [[2w1x]], [[2w1l]], [[3e3d]], [[3exd]], [[2zq3]], [[2zq4]], [[3b72]], [[3b6l]], [[2z12]], [[2z18]], [[2z19]], [[2vb1]], [[2hu3]], [[2hub]], [[2htx]], [[2hu1]], [[2yvb]], [[2epe]], [[2g4p]], [[2g4q]], [[2cgi]], [[2b5z]], [[2d4k]], [[2d91]], [[2f2n]], [[2fbb]], [[2c8o]], [[2c8p]], [[2a6u]], [[2aub]], [[2blx]], [[2bly]], [[2a7d]], [[2a7f]], [[1wtm]], [[1wtn]], [[1w6z]], [[1vdp]], [[1vdq]], [[1vds]], [[1vdt]], [[1ved]], [[1v7t]], [[1ps5]], [[2cds]], [[1lj3]], [[1lj4]], [[1lje]], [[1ljf]], [[1ljg]], [[1ljh]], [[1lji]], [[1ljj]], [[1ljk]], [[1jis]], [[1jit]], [[1jiy]], [[1jj0]], [[1jj1]], [[1jj3]], [[1iee]], [[1qio]], [[1f0w]], [[1f10]], [[1dpx]], [[1c10]], [[1qtk]], [[1lz8]], [[1lz9]], [[1bhz]], [[1bgi]], [[1bwh]], [[1bwi]], [[1bwj]], [[1bvx]], [[1hsw]], [[1hsx]], [[1lpi]], [[4lzt]], [[3lzt]], [[1aki]], [[1jpo]], [[1rfp]], [[193l]], [[194l]], [[5lym]], [[1lza]], [[3lyt]], [[4lyt]], [[5lyt]], [[6lyt]], [[2lzt]], [[1lzt]], [[1lzh]], [[2lzh]], [[7lyz]], [[1lyz]], [[2lyz]], [[3lyz]], [[4lyz]], [[5lyz]], [[6lyz]] - HEWL – chicken 
[[1xei]], [[1xej]], [[1xek]], [[1uco]], [[1lma]], [[4lym]] – HEWL low hydration 
[[1lsa]], [[1lsb]], [[1lsc]], [[1lsd]], [[1lse]], [[1lsf]], [[1lys]] – HEWL temperature influence 
[[2lym]], [[3lym]] – HEWL pressure influence 
[[132l]] – HEWL methylated 
[[1rcm]] – HEWL 3 S-S form 
[[2xbr]], [[2xbs]]- HEWL– Raman crystallography 
[[2zwb]], [[1io5]], [[1lzn]] - HEWL– Neutron 
[[1gxv]], [[1gxx]], [[1e8l]] - HEWL- NMR 
[[2hs7]], [[2hso]], [[2hs9]]- HEWL– Powder diffraction 
[[1ir7]], [[1ir8]], [[1ir9]], [[1ioq]], [[1ior]], [[1ios]], [[1iot]], [[1flq]], [[1flu]], [[1flw]], [[1fly]], [[1fn5]], [[1kxw]], [[1kxx]], [[1kxy]], [[1uia]], [[1uib]], [[1uic]], [[1uid]], [[1uie]], [[1uif]], [[1uig]], [[1uih]], [[1lsm]], [[1lsn]], [[1hel]], [[1hem]], [[1hen]], [[1heo]], [[1hep]], [[1heq]], [[1her]] – HEWL (mutant) 
[[1lyo]], [[2lyo]], [[3lyo]], [[4lyo]] – HEWL cross-linked 
[[1xft]] - tuLys – turkey - Powder diffraction 
[[1jse]], [[1tew]], [[135l]], [[2lz2]], [[1lz2]] – tuLys 
[[3lz2]] – tuLys - Laue 
[[3ab6]] – Lys + NAG3 – Hard clam 
[[2x8r]] – Lys GH25 – ''Aspergillus fumigatus'' 
[[3mgw]] – Lys G – Atlantic salmon 
[[3gxk]], [[3gxr]] – Lys G + NAG – Atlantic cod 
[[2fbd]] – HfLys 1 
[[3cb7]] – HfLys 2 
[[2zij]], [[2zik]], [[2zil]], [[2nwd]], [[1iwt]], [[1iwu]], [[1iwv]], [[1iww]], [[1iwx]], [[1iwy]], [[1iwz]], [[1jwr]], [[1jsf]], [[1rex]], [[1lz1]] – hLys – human 
[[1w08]], [[1ix0]], [[1ioc]], [[1ip1]], [[1ip2]], [[1ip3]], [[1ip4]], [[1ip5]], [[1ip6]], [[1ip7]], [[1qsw]], [[1gev]], [[1gez]], [[1gf0]], [[1gf3]], [[1gf4]], [[1gf5]], [[1gf6]], [[1gf7]], [[1i1z]], [[1i20]], [[1i22]], [[1gfr]], [[1gft]], [[1gfu]], [[1gfv]], [[1gf8]], [[1gf9]], [[1gfa]], [[1gfe]], [[1gfg]], [[1gfh]], [[1gfj]], [[1gfk]], [[1inu]], [[1gdx]], [[1ge0]], [[1ge1]], [[1ge2]], [[1ge3]], [[1ge4]], [[1gdw]], [[1gaz]], [[1gb0]], [[1gb2]], [[1gb3]], [[1gb5]], [[1gb6]], [[1gb7]], [[1gb8]], [[1gb9]], [[1gbo]], [[1gbw]], [[1gbx]], [[1gby]], [[1gbz]], [[1gay]], [[1eq4]], [[1eq5]], [[1eqe]], [[1c7p]], [[1di3]], [[1di4]], [[1di5]], [[1c43]], [[1c45]], [[1c46]], [[1ckg]], [[1cj6]], [[1cj7]], [[1cj8]], [[1cj9]], [[1ckc]], [[1ckd]], [[1ckf]], [[1ckh]], [[1b5z]], [[1b70]], [[1b7q]], [[1b7r]], [[1b7s]], [[1b7l]], [[1b7m]], [[1b7n]], [[1b7p]], [[1b5u]], [[1b5v]], [[1b5w]], [[1b5x]], [[1b5y]], [[1bb3]], [[1bb4]], [[2bqa]], [[2bqb]], [[2bqc]], [[2bqd]], [[2bqe]], [[2bqf]], [[2bqg]], [[2bqh]], [[2bqi]], [[2bqj]], [[2bqk]], [[2bql]], [[2bqm]], [[2bqn]], [[2bqo]], [[2mea]], [[2meb]], [[2mec]], [[2med]], [[2mee]], [[2mef]], [[2meg]], [[2meh]], [[2mei]], [[1wqm]], [[1wqn]], [[1wqo]], [[1wqp]], [[1wqq]], [[1wqr]], [[2heb]], [[2hea]], [[2hec]], [[2hed]], [[2hee]], [[2hef]], [[1jka]], [[1jkb]], [[1jkc]], [[1jkd]], [[1loz]], [[1lyy]], [[1oua]], [[1oub]], [[1ouc]], [[1oud]], [[1oue]], [[1ouf]], [[1oug]], [[1ouh]], [[1oui]], [[1ouj]], [[207l]], [[208l ]], [[1yam]], [[1yan]], [[1yao]], [[1yap]], [[1yaq]], [[1lmt]], [[1lhh]], [[1lhi]], [[1lhj]], [[1lhk]], [[1lhl]], [[133l]], [[134l]], [[1lz4]], [[1lz5]], [[1lz6]], [[1laa]], [[1tay]], [[1tby]], [[1tcy]], [[1tdy]], [[2lhm]], [[3lhm]] – hLys (mutant) 
[[1iy3]], [[1iy4]] – hLys - NMR 
[[2z2f]] – Lys – Bovine 
[[2cwi]], [[1el1]], [[1qqy]] – dLys - dog 
[[2z2e]] – dLys (mutant) 
[[1i56]] – dLys – NMR 
[[2dqa]] – Lys – ''Tapes japonica'' 
[[2gv0]] – Lys – Soft-shelled turtle 
[[1ivm]] – mLys M – NMR – mouse 
[[1jfx]] – Lys – ''Streptomyces coelicolor'' 
[[1gd6]] – Lys – ''Bombyx mori'' 
[[1jug]] – Lys – Echidna 
[[1dkj]] – BqLys – Bobwhite quail 
[[2ihl]] – Lys – Japanese quail 
[[1gbs]] – BsLys – Black swan 
[[1lmn]] – RtLys – Rainbow trout 
[[2eql]] – Lys – horse 
[[1ghl]] – phLys – pheasant 
[[1hhl]] – GfLys – Guinea fowl 
[[1lhm]] – Lys (mutant) – yeast 

===Lys small molecules complexes===

[[3fe0]], [[2d4i]], [[2d4j]], [[1v7s]] - HEWL+ D2O 
[[3m3u]] – HEWL Trp fluorescence 
[[2xjw]] - HEWL + CO 
[[1hf4]], [[1lks]] – HEWL + NO3 
[[3a34]], [[3ems]] - HEWL + arginine 
[[2xth]] – cLys + inhibitor K2PtBr6 
[[3a90]], [[3a91]], [[3a92]], [[3a93]], [[3a94]], [[3a95]], [[3a96]], [[3kam]], [[2pc2]], [[2bpu]], [[1t3p]], [[1h87]] – HEWL + rare earth 
[[2d6b]], [[2hg0]], [[1vat]], [[1gwd]], [[1b2k]], [[1lkr]], [[1azf]], [[8lyz]]- HEWL+ halogen 
[[1vat]] - HEWL + Xe 
[[1n4f]] - HEWL + As 
[[2i6z]] - HEWL + Pt drug 
[[2zyp]] - HEWL + poly (allyl amine) 
[[2f30]], [[2f4a]] – HEWL + urea derivative 
[[2f4g]], [[1ykx]], [[1yky]], [[1ykz]], [[1yl0]], [[1yl1]], [[1z55]] - HEWL + alcohol 
[[1dpw]] – HEWL + MPD 
[[1lcn]] – HEWL + SCN 
[[2zxs]] - HEWL with glycine-amide 
[[2h9j]], [[2h9k]], [[1yik]], [[1yil]] - HEWL + cyclam derivative 
[[1b0d]] – HEWL + p-toluene-sulfonate 
[[2q0m]] - HEWL + tricarbonylmanganese 
[[2war]] – HEWL (mutant) + chitopentaose 
[[2h5z]] – HfLys 1 + chitotetraose – House fly 
[[1hnl]] – hLys + glutathione 
[[1dkk]] – BqLys + NO3 

===Lys complex with glucoside===

[[3a3q]] – HEWL (mutant) + NAG 
[[1sf4]], [[1sf6]], [[1sf7]], [[1sfb]], [[1sfg]], [[1ja2]], [[1ja4]], [[1ja6]], [[1ja7]] – HEWL + NAG oligosaccharide – Powder diffraction 
[[1ubz]], [[1d6p]], [[1d6q]], [[1bb5]] – hLys (mutant) + glycoside 
[[1uc0]], [[1re2]], [[1rem]], [[1rey]], [[1rez]], [[1lzr]], [[1lzs]] - hLys + glycoside 
[[1ljn]], [[1jef]], [[1lzy]] – tuLys + glycoside 
[[1h6m]], [[1at5]], [[1at6]], [[1lzb]], [[1lzc]], [[1lzd]], [[1lze]], [[1lzg]], [[1hew ]]– HEWL + glycoside 
[[1lsy]], [[1lsz]] - HEWL (mutant) + glycoside 
[[1bb6]], [[1bb7]] – RtLys + glycoside 
[[1lmc]] – RtLys + bulgecin 
[[1lmo]], [[1lmp]], [[1lmq]] – RtLys + glucoside 
[[1lsp]] – BsLys + bulgecin 
[[153l]], [[154l]] – Lys +glucoside – goose 

===Phage Lys===

[[2oe4]], [[2oe7]], [[2oe9]], [[2oea]], [[1swz]], [[1cx6]], [[1qtc]], [[1qtd]], [[1qth]], [[1qsb]], [[1qs5]], [[1qs9]], [[1qtb]], [[256l]], [[206l]], [[167l]], [[168l]], [[169l]], [[170l]], [[171l]], [[172l]], [[173l]], [[174l]], [[175l]], [[176l]], [[177l]], [[178l]], [[181l]], [[182l]], [[183l]], [[184l]], [[185l]], [[186l]], [[187l]], [[188l]], [[1nhb]], [[137l]], [[216l]], [[152l]], [[149l]], [[150l]], [[151l]], [[1lyd]], [[2lzm]] - T4Lys – Enterobacteria phage T4 
[[138l]] – T4Lys cross-linked 
[[4lzm]], [[5lzm]], [[6lzm]], [[7lzm]] – T4Lys ionic strength 
[[3l2x]], [[3k2r]], [[3g3v]], [[3g3w]], [[3g3x]], [[2q9d]], [[2q9e]], [[2igc]], [[2ntg]], [[2nth]], [[2ou8]], [[2ou9]], [[1zur]], [[1zwn]], [[1zyt]], [[2cuu]], [[2a4t]] – T4Lys (mutant) spin labeled 
[[3l64]], [[3hwl]], [[3jr6]], [[3gui]], [[3c7w]], [[3c7y]], [[3c7z]], [[3c80]], [[3c81]], [[3c82]], [[3c83]], [[3c8q]], [[3c8r]], [[3c8s]], [[3cdo]], [[3cdq]], [[3cdr]], [[3cdt]], [[3cdv]], [[3f8v]], [[3f9l]], [[3fa0]], [[3fad]], [[3fi5]], [[3dke]], [[3dmv]], [[2o4w]], [[2o79]], [[2o7a]], [[2huk]], [[2hul]], [[2hum]], [[2b7x]], [[2b6t]], [[2b6w]], [[2b6x]], [[2b6y]], [[2b6z]], [[2b70]], [[2b72]], [[2b73]], [[2b74]], [[2b75]], [[1sx7]], [[1swy]], [[1sx2]], [[1t6h]], [[1ssw]], [[1ssy]], [[1t8f]], [[1t8g]], [[1t8a]], [[1t97]], [[1p56]], [[1p5c]], [[1p2l]], [[1p2r]], [[1p36]], [[1p37]], [[1p3n]], [[1p46]], [[1p64]], [[1p6y]], [[1p7s]], [[1pqd]], [[1pqi]], [[1pqj]], [[1pqk]], [[1pqm]], [[1pqo]], [[1oyu]], [[1ks3]], [[1kw5]], [[1kw7]], [[1ky0]], [[1ky1]], [[1l0j]], [[1l0k]], [[1lw9]], [[1lwg]], [[1lwk]], [[1lpy]], [[1llh]], [[1lgu]], [[1li6]], [[1jtm]], [[1jtn]], [[1jqu]], [[1kni]], [[1g06]], [[1g07]], [[1g0g]], [[1g0j]], [[1g0k]], [[1g0l]], [[1g0m]], [[1g0p]], [[1g0q]], [[1g1v]], [[1g1w]], [[1i6s]], [[257l]], [[258l]], [[260l]], [[1epy]], [[1b6i]], [[1cu6]], [[1d9w]], [[1ctw]], [[1cu0]], [[1cu2]], [[1cu3]], [[1cu5]], [[1cv1]], [[1cv4]], [[1cv5]], [[1cv6]], [[1cvk]], [[1cx7]], [[1d2w]], [[1d2y]], [[1d3f]], [[1d3j]], [[1d3m]], [[1d3n]], [[1cv3]], [[1qt3]], [[1qt4]], [[1qt5]], [[1qt6]], [[1qt7]], [[1qt8]], [[1qtv]], [[1qtz]], [[1qud]], [[1qug]], [[1quh]], [[1quo]], [[1qsq]], [[261l]], [[262l]], [[259l]], [[220l]], [[222l]], [[223l]], [[225l]], [[226l]], [[227l]], [[228l]], [[229l]], [[235l]], [[236l]], [[237l]], [[238l]], [[239l]], [[240l]], [[241l]], [[242l]], [[243l]], [[244l]], [[245l]], [[246l]], [[247l]], [[248l]], [[249l]], [[250l]], [[251l]], [[252l]], [[253l]], [[254l]], [[255l]], [[230l]], [[231l]], [[232l]], [[233l]], [[234l]], [[209l]], [[210l]], [[211l]], [[212l]], [[213l]], [[214l]], [[215l]], [[218l]], [[219l]], [[180l]], [[195l]], [[196l]], [[197l]], [[198l]], [[199l]], [[200l]], [[190l]], [[191l]], [[192l]], [[189l]], [[155l]], [[156l]], [[157l]], [[158l]], [[159l]], [[160l]], [[161l]], [[162l]], [[163l]], [[164l]], [[165l]], [[166l]], [[129l]], [[130l]], [[131l]], [[140l]], [[141l]], [[142l]], [[143l]], [[144l]], [[145l]], [[146l]], [[147l]], [[201l]], [[205l]], [[221l]], [[224l]], [[102l]], [[103l]], [[104l]], [[107l]], [[108l]], [[109l]], [[110l]], [[111l]], [[112l]], [[113l]], [[114l]], [[115l]], [[118l]], [[119l]], [[120l]], [[122l]], [[123l]], [[125l]], [[126l]], [[127l]], [[128l]], [[1dya]], [[1dyb]], [[1dyc]], [[1dyd]], [[1dye]], [[1dyf]], [[1dyg]], [[1l00]], [[1l85]], [[1l86]], [[1l87]], [[1l88]], [[1l89]], [[1l90]], [[1l91]], [[1l92]], [[1l93]], [[1l94]], [[1l95]], [[1l96]], [[1l97]], [[1l98]], [[1l99]], [[1lye]], [[1lyf]], [[1lyg]], [[1lyh]], [[1lyi]], [[1lyj]], [[217l]], [[1tla]], [[1l77]], [[1l79]], [[1l80]], [[1l81]], [[1l82]], [[2l78]], [[1l36]], [[1l37]], [[1l38]], [[1l39]], [[1l40]], [[1l41]], [[1l42]], [[1l43]], [[1l44]], [[1l45]], [[1l46]], [[1l47]], [[1l48]], [[1l49]], [[1l50]], [[1l51]], [[1l52]], [[1l53]], [[1l54]], [[1l55]], [[1l56]], [[1l57]], [[1l58]], [[1l59]], [[1l60]], [[1l61]], [[1l62]], [[1l63]], [[1l64]], [[1l65]], [[1l66]], [[1l67]], [[1l68]], [[1l69]], [[1l70]], [[1l71]], [[1l72]], [[1l73]], [[1l74]], [[1l75]], [[1l76]], [[1l17]], [[1l18]], [[1l19]], [[1l20]], [[1l21]], [[1l22]], [[1l23]], [[1l24]], [[1l25]], [[1l26]], [[1l27]], [[1l28]], [[1l29]], [[1l30]], [[1l31]], [[1l32]], [[1l33]], [[1l34]], [[1l35]], [[3lzm]], [[1l01]], [[1l02]], [[1l03]], [[1l04]], [[1l05]], [[1l06]], [[1l07]], [[1l08]], [[1l09]], [[1l10]], [[1l11]], [[1l12]], [[1l13]], [[1l14]], [[1l15]], [[1l16]] – T4Lys (mutant) 
[[1c60]], [[1c61]], [[1c62]], [[1c63]], [[1c64]], [[1c65]], [[1c66]], [[1c67]], [[1c68]], [[1c69]], [[1c6a]], [[1c6b]], [[1c6c]], [[1c6d]], [[1c6e]], [[1c6f]], [[1c6g]], [[1c6h]], [[1c6i]], [[1c6j]], [[1c6k]], [[1c6l]], [[1c6m]], [[1c6n]], [[1c6p]], [[1c6q]], [[1c6t]] - T4Lys (mutant) + noble gas 
[[3ht6]], [[3ht7]], [[3ht8]], [[3ht9]], [[3htb]], [[3hu8]], [[3huq]], [[3guj]], [[3guk]], [[3gul]], [[3gum]], [[3gun]], [[3guo]], [[3gup]], [[3dmx]], [[3dmz]], [[3dn0]], [[3dn1]], [[3dn2]], [[3dn3]], [[3dn4]], [[3dn6]], [[3dn8]], [[3dna]], [[2rb1]], [[2ray]], [[2raz]], [[2rb0]], [[2rb2]], [[2rbn]], [[2rbo]], [[2rbq]], [[2rbr]], [[2rbs]], [[2oty]],[[2otz]], [[1owy]], [[1owz]], [[1ov5]], [[1ov7]], [[1ovh]], [[1ovj]], [[1ovk]], [[1lgw]], [[1lgx]], [[1li2]], [[1li3]], [[1l83]], [[1l84]] – T4Lys (mutant) + benzene derivative 
[[3htd]], [[3htf]], [[3htg]], [[3hu9]], [[3hua]], [[3huk]], [[3hh3]], [[3hh4]], [[3hh5]], [[3hh6]], [[2rbp]], [[2ou0]], [[2f2q]], [[2f32]], [[2f47]], [[1xep]] – T4Lys (mutant) + inhibitor 
[[148l]] - T4Lys (mutant) + glucoside 
[[3d3d]], [[1d9u]] – lamLys + chitohexasaccharide 
[[1am7]] – lamLys - Enterobacteria phage λ 
[[2anv]], [[2anx]] – Lys (mutant)]] - Enterobacteria phage p22 
[[1xjt]], [[1xju]] - Lys - Enterobacteria phage p1 
[[1lba]] - T7Lys - Enterobacteria phage T7 

===Lys protein complex===

[[3m18]], [[3g3a]], [[3g3b]] - HEWL + Variable lymphocyte receptor – Marine lamprey 
[[3a67]], [[3a6b]], [[3a6c]], [[2yss]], [[2eiz]], [[2dqc]], [[2dqd]], [[2dqe]], [[2dqf]], [[2dqg]], [[2dqh]], [[2dqi]], [[2dqj]], [[1j1o]], [[1j1p]], [[1j1x]], [[1ic4]], [[1ic5]], [[1ic7]] – HEWL + mLys antibody HYHEL-10 (mutant) 
[[1xgp]], [[1xgq]], [[1xgr]], [[1xgt]], [[1xgu]] – HEWL + mLys antibody HYHEL-63 
[[3d9a]], [[2eks]], [[1ua6]], [[1c08]], [[3hfm]] – HEWL + mLys antibody HYHEL-10 
[[1uac]] - tuLys C + mLys antibody HYHEL-10 
[[1yqv]], [[2iff]] – HEWL + mLys antibody HYHEL-5 
[[1bql]] – BqLys + mLys antibody HYHEL-5 
[[1ndg]] – HEWL + mLys antibody HYHEL-8 
[[1ndm]] – HEWL + mLys antibody HYHEL-26 
[[1dqj]] - HEWL + mLys antibody HYHEL-63 
[[1nby]], [[1nbz]] – HEWL (mutant) + mLys antibody HYHEL-63 
[[1g7h]], [[1g7i]], [[1g7j]], [[1g7l]], [[1g7m]], [[1kip]], [[1kiq]], [[1kir]] – HEWL + mAnti-HEWL monoclonal antibody (mutant) 
[[1mlc]], [[1vfb]] - HEWL + mIGG1-κ D44.1 FAB 
[[1a2y]] - HEWL (mutant) + mIGG1-κ D1.3 FV 
[[1fdl]] - HEWL + mIGG1-κ D1.3 FAB 
[[1jhl]] – phLys + mIGG1-κ D11.15 FV 
[[1fbi]] – GfLys + mIGG1 F9.13.7 FAB 
[[2znw]], [[2znx]] – HEWL + hSCFV10 antibody 
[[1bvk]] - HEWL + hAnti Lys FV antibody 
[[1dzb]] – tuLys + mSCFV 1F9 
[[1zv5]], [[1zvh]], [[1zvy]], [[1zmy]], [[1ri8]], [[1rjc]], [[1xfp]], [[1jtp]], [[1jtt]], [[1jto]], [[1mel]] - HEWL + cAntibody heavy chain domain – camel 
[[1op9]] - hLys C + cAntibody heavy chain domain 
[[3otp]] – HEWL + EcProtease DO – ''Escherichia coli'' 
[[3f6z]] - HEWL + MLIC – ''Pseudomonas aeruginosa'' 
[[3eba]] – hLys C + hCABHUL6 
[[2qb0]], [[2qar]] – T4Lys/E80 TELSAM domain 
[[2i25]], [[2i26]] - HEWL +NsAntigen receptor PBLA8 variable domain – Nurse shark 
[[1sq2]], [[1t6v]] – HEWL +NsNew Antigen receptor variable domain 
[[1gpq]] – HEWL + EcInhibitor of Vertebrate Lys 
[[1aro]] – T7Lys + T7 RNA polymerase 

===Some Useful External Links===
[http://en.wikipedia.org/wiki/Lysozyme Lysozyme]

[http://en.wikipedia.org/wiki/Glycoside_hydrolase#Retaining_glycoside_hydrolases Retaining Glycoside Hydrolases]

===References===
<references/>

Alendronate

2011-03-11T12:28:14Z

Anne Goodling:

{{Template:Oberholser_Sandbox_Reservation}}


== '''Alendronate (Fosamax®)''' ==

Alendronate is commonly known for its use in treatment and prevention of osteoporosis in postmenopausal women and men, but is also used to treat Paget's disease (disease that results in deformed and enlarged bones).<ref>http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000018/</ref> Alendronate belongs to the class of nitrogen-containing bisphosphonates, which are inorganic pyrophosphate analogues.

== History of Bisphosphonates ==

Bisphosphonates were first synthesized in Germany in 1865, but were not studied biologically until 1968. In the interim time, they were used in the textile and fertilizer industries due to their apparent inhibitory effect on calcium carbonate. However, in 1968, a group in Switzerland found inorganic pyrophosphates in urine and plasma. In vitro testing of these molecules revealed that they inhibited calcium phosphate precipitation and dissolution, but were destroyed in vivo by phosphatases. These results led to the discovery of bisphosphonates, as they reacted in the prescribed manner.<ref>http://www.ncbi.nlm.nih.gov/pmc/articles/PMC138713/?tool=pmcentrez</ref>

Sodium alendronate was first marketed in 1994 as Fosamax® by Merck pharmaceutical. In 2008, Merck lost their U.S. patent on alendronate, allowing Barr Pharmaceuticals and Teva Pharmaceuticals USA to begin marketing generic forms of sodium alendronate. Other brand names for the drug include Fosamax+D®, Adronat, Alendros, Arendal, and Onclast.<ref>http://www.drugbank.ca/drugs/DB00630</ref>

== Structure and General Function ==
[[Image:Alendronate.gif]]<ref>Image from: http://pharmacy-and-drugs.com</ref>

Alendronate is an aminobisphosphonate with a nonhydrolyzable P-C-P. It is structurally similar to IPP, which is pictured further down the page, and thus can bind to FPPS in place of IPP. Alendronate generally affects the activity of osteoclasts in bone. Osteoclasts are responsible for breaking down bone and also for bone resorption (losing bone substance). <ref>http://www.medterms.com/script/main/art.asp?articlekey=11794</ref> When alendronate is present, bone resorption is inhibited and bone breakdown is diminished.

== Side affects of Drug ==

Possible side affects for Fosamax include nausea,stomach pain, constipation, diarrhea, gas, bloating or fullness in the stomach, change in ability to taste food, headache, dizziness, and swelling of the joints, hands, or legs. More serious side effects (symptoms requiring doctor involvement) include new or worsening heartburn, difficulty swallowing, pain on swallowing, chest pain, bloody vomit or vomit that looks like coffee grounds, black, tarry, or bloody stools, fever, blisters or peeling skin, rash (may be made worse by sunlight), itching, hives, swelling of eyes, face, lips, tongue, or throat, difficulty breathing, hoarseness, painful or swollen gums, loosening of the teeth, numbness or heavy feeling in the jaw, poor healing of the jaw, and eye pain.<ref>http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000018/</ref>

Fosamax has also been linked to sudden subtrochanteric and diaphyseal femur fractures, osteonecrosis of the jaw, and esophageal disorders.<ref>http://fosamax.legalview.info/</ref>

== Target Proteins and Bone ==

Alendronate not only targets several proteins, but also directly binds to a bone mineral (hydroxyapatite), which causes the inhibition of bone resorption. The alendronate is bound to hydroxypatite and taken up into the osteoclsat during bone resorption.<ref>http://www.ncbi.nlm.nih.gov/pubmed/20209564</ref><ref>http://www.ncbi.nlm.nih.gov/pubmed/16046206</ref>

=== Protein-Tyrosine-Phosphatases (PTP) ===

Protein-Tyrosine-Phosphatses (PTPs) are reported to have an effect on osteoclast formation and function. Initial reports indicated that alendronate inhibited several types of PTPs, though specific mechanisms are not known. The data does suggest that alendronate works as an antagonist, which means that, when bound, the alendronate does not elicit a response from the protein but rather disallows the binding of an agonist which would cause a change (likely activating) in the protein.<ref>http://www.drugbank.ca/drugs/DB00630</ref><ref>http://www.ncbi.nlm.nih.gov/pubmed/8610169</ref><ref>http://www.ncbi.nlm.nih.gov/pubmed/9310349</ref> A
<scene name='Sandbox_59/Ptpre/1'>PTP example</scene> is given, so the binding site can be seen.

<Structure load='2f92' size='450' frame='true' align='right' caption='Shown: The asymmetric subunit of FPPS, not the assumed biological molecule.' scene='Insert optional scene name here' />
=== Farnesyl Pyrophosphate Synthase (FPPS) ===

<scene name='Sandbox_59/Fpps/3'>Farnesyl pyrophosphate synthase (FPPS)</scene> is considered the main target protein of aminobisphosphonates (including alendronate). FPPS is the prenyl transferase in the HMG-CoA Reductase Pathway, which forms cholesterol (sterols and terpenoids) from acetyl CoA. It reacts with 3-isopentenyl pyrophosphate (IPP) to form geranyl pyrophosphate (GGP). Researchers discovered that alendronate inhibits FPPS because they found a build-up of IPP in the cell, but less GGP.<ref>http://www.ncbi.nlm.nih.gov/pubmed/10620343</ref>

The FPPS mechanism can be seen below:
[[Image:FPPS Mechanism.gif]]

The identified mechanism of alendronate on FPPS begins with the absorption of the alendronate into the osteoclast via binding to hydroxyapatite. Once in the osteoclast, the <scene name='Sandbox_59/Active_site_ligand_space_fill/2'>alendronate binds</scene> to the active site of FPPS.<ref>Fisher et. all. ''Alendronate mechanism of action: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro''.Cell Biology, Vol. 96, pp. 133–138, January 1999</ref> In the active site, it appears that the alendronate interacts directly with <scene name='Sandbox_59/Active_site_ligand/2'>three Asp residues</scene>, not allowing the IPP to bind, and effectively daectivating FPPS.

The deactivation of FPPS causes a disruption of prenylation in the cell and thus affects various GTPases. For instance, it will incorrectly activate the GTPases Rho, Rac, and Cdc42.<ref>http://www.ncbi.nlm.nih.gov/pubmed/16734383</ref> The inhibition of post-translational prenylation of Ras is likely to cause cell apoptosis. <ref>http://www.ncbi.nlm.nih.gov/pubmed/9556058</ref>

==== FPPS Substrate ====

[[Image:IPP.png]]<ref>Image from: http://reference.findtarget.com</ref>

Isopentenyl pyrophosphate (IPP) actually binds to and stabilizes the alendronate-FPPS complex, rather than competing with the inhibitor.<ref>http://www.rcsb.org/pdb/explore/explore.do?structureId=2F92</ref> IPP can be seen in complex with FPPS and zoledronate
<scene name='Sandbox_59/Ipp_and_zol/2'>here</scene>. (Zoledronate is also an aminobisphosphonate)

== References ==

<references/>

Alendronate

2011-03-11T12:16:35Z

Anne Goodling:

{{Template:Oberholser_Sandbox_Reservation}}


== '''Alendronate (Fosamax®)''' ==

Alendronate is commonly known for its use in treatment and prevention of osteoporosis in postmenopausal women and men, but is also used to treat Paget's disease (disease that results in deformed and enlarged bones).<ref>http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000018/</ref> Alendronate belongs to the class of nitrogen-containing bisphosphonates, which are inorganic pyrophosphate analogues.

== History of Bisphosphonates ==

Bisphosphonates were first synthesized in Germany in 1865, but were not studied biologically until 1968. In the interim time, they were used in the textile and fertilizer industries due to their apparent inhibitory effect on calcium carbonate. However, in 1968, a group in Switzerland found inorganic pyrophosphates in urine and plasma. In vitro testing of these molecules revealed that they inhibited calcium phosphate precipitation and dissolution, but were destroyed in vivo by phosphatases. These results led to the discovery of bisphosphonates, as they reacted in the prescribed manner.<ref>http://www.ncbi.nlm.nih.gov/pmc/articles/PMC138713/?tool=pmcentrez</ref>

Sodium alendronate was first marketed in 1994 as Fosamax® by Merck pharmaceutical. In 2008, Merck lost their U.S. patent on alendronate, allowing Barr Pharmaceuticals and Teva Pharmaceuticals USA to begin marketing generic forms of sodium alendronate. Other brand names for the drug include Fosamax+D®, Adronat, Alendros, Arendal, and Onclast.<ref>http://www.drugbank.ca/drugs/DB00630</ref>

== Structure and General Function ==
[[Image:Alendronate.gif]]<ref>Image from: http://pharmacy-and-drugs.com</ref>

Alendronate is an aminobisphosphonate with a nonhydrolyzable P-C-P. Alendronate generally affects the activity of osteoclasts in bone. Osteoclasts are responsible for breaking down bone and also for bone resorption (losing bone substance). <ref>http://www.medterms.com/script/main/art.asp?articlekey=11794</ref> When alendronate is present, bone resorption is inhibited and bone breakdown is diminished.

== Side affects of Drug ==

Possible side affects for Fosamax include nausea,stomach pain, constipation, diarrhea, gas, bloating or fullness in the stomach, change in ability to taste food, headache, dizziness, and swelling of the joints, hands, or legs. More serious side effects (symptoms requiring doctor involvement) include new or worsening heartburn, difficulty swallowing, pain on swallowing, chest pain, bloody vomit or vomit that looks like coffee grounds, black, tarry, or bloody stools, fever, blisters or peeling skin, rash (may be made worse by sunlight), itching, hives, swelling of eyes, face, lips, tongue, or throat, difficulty breathing, hoarseness, painful or swollen gums, loosening of the teeth, numbness or heavy feeling in the jaw, poor healing of the jaw, and eye pain.<ref>http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000018/</ref>

Fosamax has also been linked to sudden subtrochanteric and diaphyseal femur fractures, osteonecrosis of the jaw, and esophageal disorders.<ref>http://fosamax.legalview.info/</ref>

== Target Proteins and Bone ==

Alendronate not only targets several proteins, but also directly binds to a bone mineral (hydroxyapatite), which causes the inhibition of bone resorption. The alendronate is bound to hydroxypatite and taken up into the osteoclsat during bone resorption.<ref>http://www.ncbi.nlm.nih.gov/pubmed/20209564</ref><ref>http://www.ncbi.nlm.nih.gov/pubmed/16046206</ref>

=== Protein-Tyrosine-Phosphatases (PTP) ===

Protein-Tyrosine-Phosphatses (PTPs) are reported to have an effect on osteoclast formation and function. Initial reports indicated that alendronate inhibited several types of PTPs, though specific mechanisms are not known. The data does suggest that alendronate works as an antagonist, which means that, when bound, the alendronate does not elicit a response from the protein but rather disallows the binding of an agonist which would cause a change (likely activating) in the protein.<ref>http://www.drugbank.ca/drugs/DB00630</ref><ref>http://www.ncbi.nlm.nih.gov/pubmed/8610169</ref><ref>http://www.ncbi.nlm.nih.gov/pubmed/9310349</ref> A
<scene name='Sandbox_59/Ptpre/1'>PTP example</scene> is given, so the binding site can be seen.

<Structure load='2f92' size='450' frame='true' align='right' caption='Shown: The asymmetric subunit of FPPS, not the assumed biological molecule.' scene='Insert optional scene name here' />
=== Farnesyl Pyrophosphate Synthase (FPPS) ===

<scene name='Sandbox_59/Fpps/3'>Farnesyl pyrophosphate synthase (FPPS)</scene> is considered the main target protein of aminobisphosphonates (including alendronate). FPPS is the prenyl transferase in the HMG-CoA Reductase Pathway, which forms cholesterol (sterols and terpenoids) from acetyl CoA. It reacts with 3-isopentenyl pyrophosphate (IPP) to form geranyl pyrophosphate (GGP). Researchers discovered that alendronate inhibits FPPS because they found a build-up of IPP in the cell, but less GGP.<ref>http://www.ncbi.nlm.nih.gov/pubmed/10620343</ref>

The FPPS mechanism can be seen below:
[[Image:FPPS Mechanism.gif]]

The identified mechanism of alendronate on FPPS begins with the absorption of the alendronate into the osteoclast via binding to hydroxyapatite. Once in the osteoclast, the <scene name='Sandbox_59/Active_site_ligand_space_fill/2'>alendronate binds</scene> to the active site of FPPS.<ref>Fisher et. all. ''Alendronate mechanism of action: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro''.Cell Biology, Vol. 96, pp. 133–138, January 1999</ref> In the active site, it appears that the alendronate interacts directly with <scene name='Sandbox_59/Active_site_ligand/2'>three Asp residues</scene>, not allowing the IPP to bind, and effectively daectivating FPPS.

The deactivation of FPPS causes a disruption of prenylation in the cell and thus affects various GTPases. For instance, it will incorrectly activate the GTPases Rho, Rac, and Cdc42.<ref>http://www.ncbi.nlm.nih.gov/pubmed/16734383</ref> The inhibition of post-translational prenylation of Ras is likely to cause cell apoptosis. <ref>http://www.ncbi.nlm.nih.gov/pubmed/9556058</ref>

==== FPPS Substrate ====

[[Image:IPP.png]]<ref>Image from: http://reference.findtarget.com</ref>

Isopentenyl pyrophosphate (IPP) actually binds to and stabilizes the alendronate-FPPS complex, rather than competing with the inhibitor.

== References ==

<references/>

Alendronate

2011-03-11T12:15:25Z

Anne Goodling:

{{Template:Oberholser_Sandbox_Reservation}}


== '''Alendronate (Fosamax®)''' ==

Alendronate is commonly known for its use in treatment and prevention of osteoporosis in postmenopausal women and men, but is also used to treat Paget's disease (disease that results in deformed and enlarged bones).<ref>http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000018/</ref> Alendronate belongs to the class of nitrogen-containing bisphosphonates, which are inorganic pyrophosphate analogues.

== History of Bisphosphonates ==

Bisphosphonates were first synthesized in Germany in 1865, but were not studied biologically until 1968. In the interim time, they were used in the textile and fertilizer industries due to their apparent inhibitory effect on calcium carbonate. However, in 1968, a group in Switzerland found inorganic pyrophosphates in urine and plasma. In vitro testing of these molecules revealed that they inhibited calcium phosphate precipitation and dissolution, but were destroyed in vivo by phosphatases. These results led to the discovery of bisphosphonates, as they reacted in the prescribed manner.<ref>http://www.ncbi.nlm.nih.gov/pmc/articles/PMC138713/?tool=pmcentrez</ref>

Sodium alendronate was first marketed in 1994 as Fosamax® by Merck pharmaceutical. In 2008, Merck lost their U.S. patent on alendronate, allowing Barr Pharmaceuticals and Teva Pharmaceuticals USA to begin marketing generic forms of sodium alendronate. Other brand names for the drug include Fosamax+D®, Adronat, Alendros, Arendal, and Onclast.<ref>http://www.drugbank.ca/drugs/DB00630</ref>

== Structure and General Function ==
[[Image:Alendronate.gif]]<ref>Image from: http://pharmacy-and-drugs.com</ref>

Alendronate is an aminobisphosphonate with a nonhydrolyzable P-C-P. Alendronate generally affects the activity of osteoclasts in bone. Osteoclasts are responsible for breaking down bone and also for bone resorption (losing bone substance). <ref>http://www.medterms.com/script/main/art.asp?articlekey=11794</ref> When alendronate is present, bone resorption is inhibited and bone breakdown is diminished.

== Side affects of Drug ==

Possible side affects for Fosamax include nausea,stomach pain, constipation, diarrhea, gas, bloating or fullness in the stomach, change in ability to taste food, headache, dizziness, and swelling of the joints, hands, or legs. More serious side effects (symptoms requiring doctor involvement) include new or worsening heartburn, difficulty swallowing, pain on swallowing, chest pain, bloody vomit or vomit that looks like coffee grounds, black, tarry, or bloody stools, fever, blisters or peeling skin, rash (may be made worse by sunlight), itching, hives, swelling of eyes, face, lips, tongue, or throat, difficulty breathing, hoarseness, painful or swollen gums, loosening of the teeth, numbness or heavy feeling in the jaw, poor healing of the jaw, and eye pain.<ref>http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000018/</ref>

Fosamax has also been linked to sudden subtrochanteric and diaphyseal femur fractures, osteonecrosis of the jaw, and esophageal disorders.<ref>http://fosamax.legalview.info/</ref>

== Target Proteins and Bone ==

Alendronate not only targets several proteins, but also directly binds to a bone mineral (hydroxyapatite), which causes the inhibition of bone resorption. The alendronate is bound to hydroxypatite and taken up into the osteoclsat during bone resorption.<ref>http://www.ncbi.nlm.nih.gov/pubmed/20209564</ref><ref>http://www.ncbi.nlm.nih.gov/pubmed/16046206</ref>

=== Protein-Tyrosine-Phosphatases (PTP) ===

Protein-Tyrosine-Phosphatses (PTPs) are reported to have an effect on osteoclast formation and function. Initial reports indicated that alendronate inhibited several types of PTPs, though specific mechanisms are not known. The data does suggest that alendronate works as an antagonist, which means that, when bound, the alendronate does not elicit a response from the protein but rather disallows the binding of an agonist which would cause a change (likely activating) in the protein.<ref>http://www.drugbank.ca/drugs/DB00630</ref><ref>http://www.ncbi.nlm.nih.gov/pubmed/8610169</ref><ref>http://www.ncbi.nlm.nih.gov/pubmed/9310349</ref> A
<scene name='Sandbox_59/Ptpre/1'>PTP example</scene> is given, so the binding site can be seen.

<Structure load='2f92' size='450' frame='true' align='right' caption='Shown: The asymmetric subunit of FPPS, not the assumed biological molecule.' scene='Insert optional scene name here' />
=== Farnesyl Pyrophosphate Synthase (FPPS) ===

<scene name='Sandbox_59/Fpps/3'>Farnesyl pyrophosphate synthase (FPPS)</scene> is considered the main target protein of aminobisphosphonates (including alendronate). FPPS is the prenyl transferase in the HMG-CoA Reductase Pathway, which forms cholesterol (sterols and terpenoids) from acetyl CoA. It reacts with 3-isopentenyl pyrophosphate (IPP) to form geranyl pyrophosphate (GGP). Researchers discovered that alendronate inhibits FPPS because they found a build-up of IPP in the cell, but less GGP.<ref>http://www.ncbi.nlm.nih.gov/pubmed/10620343</ref>

The FPPS mechanism can be seen below:
[[Image:FPPS Mechanism.gif]]

The identified mechanism of alendronate on FPPS begins with the absorption of the alendronate into the osteoclast via binding to hydroxyapatite. Once in the osteoclast, the <scene name='Sandbox_59/Active_site_ligand_space_fill/2'>alendronate binds</scene> to the active site of FPPS.<ref>Fisher et. all. ''Alendronate mechanism of action: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro''.Cell Biology, Vol. 96, pp. 133–138, January 1999</ref> In the active site, it appears that the alendronate interacts directly with <scene name='Sandbox_59/Active_site_ligand/2'>three Asp residues</scene>, not allowing the IPP to bind, and effectively daectivating FPPS.

The deactivation of FPPS causes a disruption of prenylation in the cell and thus affects various GTPases. For instance, it will incorrectly activate the GTPases Rho, Rac, and Cdc42.<ref>http://www.ncbi.nlm.nih.gov/pubmed/16734383</ref> The inhibition of post-translational prenylation of Ras is likely to cause cell apoptosis. <ref>http://www.ncbi.nlm.nih.gov/pubmed/9556058</ref>

==== FPPS Substrate ====

[[Image:IPP.png]]<ref>Image from: http://reference.findtarget.com</ref>

Isopentenyl pyrophosphate (IPP) actually binds to and stabilizes the alendronate-FPPS complex, rather than competing with the inhibitor.

== References ==

<references/>

File:FPPS Mechanism.gif

2011-03-11T12:13:25Z

Anne Goodling:

Alendronate

2011-03-11T12:08:52Z

Anne Goodling:

{{Template:Oberholser_Sandbox_Reservation}}


== '''Alendronate (Fosamax®)''' ==

Alendronate is commonly known for its use in treatment and prevention of osteoporosis in postmenopausal women and men, but is also used to treat Paget's disease (disease that results in deformed and enlarged bones).<ref>http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000018/</ref> Alendronate belongs to the class of nitrogen-containing bisphosphonates, which are inorganic pyrophosphate analogues.

== History of Bisphosphonates ==

Bisphosphonates were first synthesized in Germany in 1865, but were not studied biologically until 1968. In the interim time, they were used in the textile and fertilizer industries due to their apparent inhibitory effect on calcium carbonate. However, in 1968, a group in Switzerland found inorganic pyrophosphates in urine and plasma. In vitro testing of these molecules revealed that they inhibited calcium phosphate precipitation and dissolution, but were destroyed in vivo by phosphatases. These results led to the discovery of bisphosphonates, as they reacted in the prescribed manner.<ref>http://www.ncbi.nlm.nih.gov/pmc/articles/PMC138713/?tool=pmcentrez</ref>

Sodium alendronate was first marketed in 1994 as Fosamax® by Merck pharmaceutical. In 2008, Merck lost their U.S. patent on alendronate, allowing Barr Pharmaceuticals and Teva Pharmaceuticals USA to begin marketing generic forms of sodium alendronate. Other brand names for the drug include Fosamax+D®, Adronat, Alendros, Arendal, and Onclast.<ref>http://www.drugbank.ca/drugs/DB00630</ref>

== Structure and General Function ==
[[Image:Alendronate.gif]]<ref>Image from: http://pharmacy-and-drugs.com</ref>

Alendronate is an aminobisphosphonate with a nonhydrolyzable P-C-P. Alendronate generally affects the activity of osteoclasts in bone. Osteoclasts are responsible for breaking down bone and also for bone resorption (losing bone substance). <ref>http://www.medterms.com/script/main/art.asp?articlekey=11794</ref> When alendronate is present, bone resorption is inhibited and bone breakdown is diminished.

== Side affects of Drug ==

Possible side affects for Fosamax include nausea,stomach pain, constipation, diarrhea, gas, bloating or fullness in the stomach, change in ability to taste food, headache, dizziness, and swelling of the joints, hands, or legs. More serious side effects (symptoms requiring doctor involvement) include new or worsening heartburn, difficulty swallowing, pain on swallowing, chest pain, bloody vomit or vomit that looks like coffee grounds, black, tarry, or bloody stools, fever, blisters or peeling skin, rash (may be made worse by sunlight), itching, hives, swelling of eyes, face, lips, tongue, or throat, difficulty breathing, hoarseness, painful or swollen gums, loosening of the teeth, numbness or heavy feeling in the jaw, poor healing of the jaw, and eye pain.<ref>http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000018/</ref>

Fosamax has also been linked to sudden subtrochanteric and diaphyseal femur fractures, osteonecrosis of the jaw, and esophageal disorders.<ref>http://fosamax.legalview.info/</ref>

== Target Proteins and Bone ==

Alendronate not only targets several proteins, but also directly binds to a bone mineral (hydroxyapatite), which causes the inhibition of bone resorption. The alendronate is bound to hydroxypatite and taken up into the osteoclsat during bone resorption.<ref>http://www.ncbi.nlm.nih.gov/pubmed/20209564</ref><ref>http://www.ncbi.nlm.nih.gov/pubmed/16046206</ref>

=== Protein-Tyrosine-Phosphatases (PTP) ===

Protein-Tyrosine-Phosphatses (PTPs) are reported to have an effect on osteoclast formation and function. Initial reports indicated that alendronate inhibited several types of PTPs, though specific mechanisms are not known. The data does suggest that alendronate works as an antagonist, which means that, when bound, the alendronate does not elicit a response from the protein but rather disallows the binding of an agonist which would cause a change (likely activating) in the protein.<ref>http://www.drugbank.ca/drugs/DB00630</ref><ref>http://www.ncbi.nlm.nih.gov/pubmed/8610169</ref><ref>http://www.ncbi.nlm.nih.gov/pubmed/9310349</ref> A
<scene name='Sandbox_59/Ptpre/1'>PTP example</scene> is given, so the binding site can be seen.

<Structure load='2f92' size='450' frame='true' align='right' caption='Shown: The asymmetric subunit of FPPS, not the assumed biological molecule.' scene='Insert optional scene name here' />
=== Farnesyl Pyrophosphate Synthase (FPPS) ===

<scene name='Sandbox_59/Fpps/3'>Farnesyl pyrophosphate synthase (FPPS)</scene> is considered the main target protein of aminobisphosphonates (including alendronate). FPPS is the prenyl transferase in the HMG-CoA Reductase Pathway, which forms cholesterol (sterols and terpenoids) from acetyl CoA. It reacts with 3-isopentenyl pyrophosphate (IPP) to form geranyl pyrophosphate (GGP). Researchers discovered that alendronate inhibits FPPS because they found a build-up of IPP in the cell, but less GGP.<ref>http://www.ncbi.nlm.nih.gov/pubmed/10620343</ref>

The identified mechanism of alendronate on FPPS begins with the absorption of the alendronate into the osteoclast via binding to hydroxyapatite. Once in the osteoclast, the <scene name='Sandbox_59/Active_site_ligand_space_fill/2'>alendronate binds</scene> to the active site of FPPS.<ref>Fisher et. all. ''Alendronate mechanism of action: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro''.Cell Biology, Vol. 96, pp. 133–138, January 1999</ref> In the active site, it appears that the alendronate interacts directly with <scene name='Sandbox_59/Active_site_ligand/2'>three Asp residues</scene>, not allowing the IPP to bind, and effectively daectivating FPPS.

The deactivation of FPPS causes a disruption of prenylation in the cell and thus affects various GTPases. For instance, it will incorrectly activate the GTPases Rho, Rac, and Cdc42.<ref>http://www.ncbi.nlm.nih.gov/pubmed/16734383</ref> The inhibition of post-translational prenylation of Ras is likely to cause cell apoptosis. <ref>http://www.ncbi.nlm.nih.gov/pubmed/9556058</ref>

==== FPPS Substrate ====

[[Image:IPP.png]]<ref>Image from: http://reference.findtarget.com</ref>

Isopentenyl pyrophosphate (IPP) actually binds to and stabilizes the alendronate-FPPS complex, rather than competing with the inhibitor.

== References ==

<references/>

Alendronate

2011-03-11T12:02:33Z

Anne Goodling:

{{Template:Oberholser_Sandbox_Reservation}}


== '''Alendronate (Fosamax®)''' ==

Alendronate is commonly known for its use in treatment and prevention of osteoporosis in postmenopausal women and men, but is also used to treat Paget's disease (disease that results in deformed and enlarged bones).<ref>http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000018/</ref> Alendronate belongs to the class of nitrogen-containing bisphosphonates, which are inorganic pyrophosphate analogues.

== History of Bisphosphonates ==

Bisphosphonates were first synthesized in Germany in 1865, but were not studied biologically until 1968. In the interim time, they were used in the textile and fertilizer industries due to their apparent inhibitory effect on calcium carbonate. However, in 1968, a group in Switzerland found inorganic pyrophosphates in urine and plasma. In vitro testing of these molecules revealed that they inhibited calcium phosphate precipitation and dissolution, but were destroyed in vivo by phosphatases. These results led to the discovery of bisphosphonates, as they reacted in the prescribed manner.<ref>http://www.ncbi.nlm.nih.gov/pmc/articles/PMC138713/?tool=pmcentrez</ref>

Sodium alendronate was first marketed in 1994 as Fosamax® by Merck pharmaceutical. In 2008, Merck lost their U.S. patent on alendronate, allowing Barr Pharmaceuticals and Teva Pharmaceuticals USA to begin marketing generic forms of sodium alendronate. Other brand names for the drug include Fosamax+D®, Adronat, Alendros, Arendal, and Onclast.<ref>http://www.drugbank.ca/drugs/DB00630</ref>

== Structure and General Function ==
[[Image:Alendronate.gif]]<ref>Image from: http://pharmacy-and-drugs.com</ref>

Alendronate is an aminobisphosphonate with a nonhydrolyzable P-C-P. Alendronate generally affects the activity of osteoclasts in bone. Osteoclasts are responsible for breaking down bone and also for bone resorption (losing bone substance). <ref>http://www.medterms.com/script/main/art.asp?articlekey=11794</ref> When alendronate is present, bone resorption is inhibited and bone breakdown is diminished.

== Side affects of Drug ==

Possible side affects for Fosamax include nausea,stomach pain, constipation, diarrhea, gas, bloating or fullness in the stomach, change in ability to taste food, headache, dizziness, and swelling of the joints, hands, or legs. More serious side effects (symptoms requiring doctor involvement) include new or worsening heartburn, difficulty swallowing, pain on swallowing, chest pain, bloody vomit or vomit that looks like coffee grounds, black, tarry, or bloody stools, fever, blisters or peeling skin, rash (may be made worse by sunlight), itching, hives, swelling of eyes, face, lips, tongue, or throat, difficulty breathing, hoarseness, painful or swollen gums, loosening of the teeth, numbness or heavy feeling in the jaw, poor healing of the jaw, and eye pain.<ref>http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000018/</ref>

Fosamax has also been linked to sudden subtrochanteric and diaphyseal femur fractures, osteonecrosis of the jaw, and esophageal disorders.<ref>http://fosamax.legalview.info/</ref>

== Target Proteins and Bone ==

Alendronate not only targets several proteins, but also directly binds to a bone mineral (hydroxyapatite), which causes the inhibition of bone resorption. The alendronate is bound to hydroxypatite and taken up into the osteoclsat during bone resorption.<ref>http://www.ncbi.nlm.nih.gov/pubmed/20209564</ref><ref>http://www.ncbi.nlm.nih.gov/pubmed/16046206</ref>

=== Protein-Tyrosine-Phosphatases (PTP) ===

Protein-Tyrosine-Phosphatses (PTPs) are reported to have an effect on osteoclast formation and function. Initial reports indicated that alendronate inhibited several types of PTPs, though specific mechanisms are not known. The data does suggest that alendronate works as an antagonist, which means that, when bound, the alendronate does not elicit a response from the protein but rather disallows the binding of an agonist which would cause a change (likely activating) in the protein.<ref>http://www.drugbank.ca/drugs/DB00630</ref><ref>http://www.ncbi.nlm.nih.gov/pubmed/8610169</ref><ref>http://www.ncbi.nlm.nih.gov/pubmed/9310349</ref> A
<scene name='Sandbox_59/Ptpre/1'>PTP example</scene> is given, so the binding site can be seen.

=== Farnesyl Pyrophosphate Synthase (FPPS) ===
<Structure load='2f92' size='450' frame='true' align='right' caption='Shown: The asymmetric subunit of FPPS, not the assumed biological molecule.' scene='Insert optional scene name here' />

<scene name='Sandbox_59/Fpps/3'>Farnesyl pyrophosphate synthase (FPPS)</scene> is considered the main target protein of aminobisphosphonates (including alendronate). FPPS is the prenyl transferase in the HMG-CoA Reductase Pathway, which forms cholesterol (sterols and terpenoids) from acetyl CoA. It reacts with 3-isopentenyl pyrophosphate (IPP) to form geranyl pyrophosphate (GGP). Researchers discovered that alendronate inhibits FPPS because they found a build-up of IPP in the cell, but less GGP.<ref>http://www.ncbi.nlm.nih.gov/pubmed/10620343</ref>

The identified mechanism of alendronate on FPPS begins with the absorption of the alendronate into the osteoclast via binding to hydroxyapatite. Once in the osteoclast, the <scene name='Sandbox_59/Active_site_ligand_space_fill/2'>alendronate binds</scene> to the active site of FPPS.<ref>Fisher et. all. ''Alendronate mechanism of action: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro''.Cell Biology, Vol. 96, pp. 133–138, January 1999</ref> In the active site, it appears that the alendronate interacts directly with <scene name='Sandbox_59/Active_site_ligand/2'>three Asp residues</scene>, not allowing the IPP to bind, and effectively daectivating FPPS.

The deactivation of FPPS causes a disruption of prenylation in the cell and thus affects various GTPases. For instance, it will incorrectly activate the GTPases Rho, Rac, and Cdc42.<ref>http://www.ncbi.nlm.nih.gov/pubmed/16734383</ref> The inhibition of post-translational prenylation of Ras is likely to cause cell apoptosis. <ref>http://www.ncbi.nlm.nih.gov/pubmed/9556058</ref>

==== FPPS Substrate ====

[[Image:IPP.png]]<ref>Image from: http://reference.findtarget.com</ref>

Isopentenyl pyrophosphate (IPP) actually binds to and stabilizes the alendronate-FPPS complex, rather than competing with the inhibitor.

== References ==

<references/>

Alendronate

2011-03-11T11:42:14Z

Anne Goodling: /* FPPS Natural Substrates */

{{Template:Oberholser_Sandbox_Reservation}}


== '''Alendronate (Fosamax®)''' ==

Alendronate is commonly known for its use in treatment and prevention of osteoporosis in postmenopausal women and men, but is also used to treat Paget's disease (disease that results in deformed and enlarged bones).<ref>http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000018/</ref> Alendronate belongs to the class of nitrogen-containing bisphosphonates, which are inorganic pyrophosphate analogues.

== History of Bisphosphonates ==

Bisphosphonates were first synthesized in Germany in 1865, but were not studied biologically until 1968. In the interim time, they were used in the textile and fertilizer industries due to their apparent inhibitory effect on calcium carbonate. However, in 1968, a group in Switzerland found inorganic pyrophosphates in urine and plasma. In vitro testing of these molecules revealed that they inhibited calcium phosphate precipitation and dissolution, but were destroyed in vivo by phosphatases. These results led to the discovery of bisphosphonates, as they reacted in the prescribed manner.<ref>http://www.ncbi.nlm.nih.gov/pmc/articles/PMC138713/?tool=pmcentrez</ref>

Sodium alendronate was first marketed in 1994 as Fosamax® by Merck pharmaceutical. In 2008, Merck lost their U.S. patent on alendronate, allowing Barr Pharmaceuticals and Teva Pharmaceuticals USA to begin marketing generic forms of sodium alendronate. Other brand names for the drug include Fosamax+D®, Adronat, Alendros, Arendal, and Onclast.<ref>http://www.drugbank.ca/drugs/DB00630</ref>

== Structure and General Function ==
[[Image:Alendronate.gif]]<ref>Image from: http://pharmacy-and-drugs.com</ref>

Alendronate is an aminobisphosphonate with a nonhydrolyzable P-C-P. Alendronate generally affects the activity of osteoclasts in bone. Osteoclasts are responsible for breaking down bone and also for bone resorption (losing bone substance). <ref>http://www.medterms.com/script/main/art.asp?articlekey=11794</ref> When alendronate is present, bone resorption is inhibited and bone breakdown is diminished.

== Target Proteins and Bone ==

Alendronate not only targets several proteins, but also directly binds to a bone mineral (hydroxyapatite), which causes the inhibition of bone resorption. The alendronate is bound to hydroxypatite and taken up into the osteoclsat during bone resorption.<ref>http://www.ncbi.nlm.nih.gov/pubmed/20209564</ref><ref>http://www.ncbi.nlm.nih.gov/pubmed/16046206</ref>

=== Protein-Tyrosine-Phosphatases (PTP) ===

Protein-Tyrosine-Phosphatses (PTPs) are reported to have an effect on osteoclast formation and function.<ref>
<scene name='Sandbox_59/Ptpre/1'>TextToBeDisplayed</scene></ref> Initial reports indicated that alendronate inhibited several types of PTPs, though specific mechanisms are not known. The data does suggest that alendronate works as an antagonist, which means that, when bound, the alendronate does not elicit a response from the protein but rather disallows the binding of an agonist which would cause a change (likely activating) in the protein.<ref>http://www.drugbank.ca/drugs/DB00630</ref><ref>http://www.ncbi.nlm.nih.gov/pubmed/8610169</ref><ref>http://www.ncbi.nlm.nih.gov/pubmed/9310349</ref> A
<scene name='Sandbox_59/Ptpre/1'>PTP example</scene> is given, so the binding site can be seen.

=== Farnesyl Pyrophosphate Synthase (FPPS) ===
<Structure load='2f92' size='450' frame='true' align='right' caption='Shown: The asymmetric subunit of FPPS, not the assumed biological molecule.' scene='Insert optional scene name here' />

<scene name='Sandbox_59/Fpps/3'>Farnesyl pyrophosphate synthase (FPPS)</scene> is considered the main target protein of aminobisphosphonates (including alendronate). FPPS is the prenyl transferase in the HMG-CoA Reductase Pathway, which forms cholesterol (sterols and terpenoids) from acetyl CoA. It reacts with 3-isopentenyl pyrophosphate (IPP) to form geranyl pyrophosphate (GGP). Researchers discovered that alendronate inhibits FPPS because they found a build-up of IPP in the cell, but less GGP.<ref>http://www.ncbi.nlm.nih.gov/pubmed/10620343</ref>

The identified mechanism of alendronate on FPPS begins with the absorption of the alendronate into the osteoclast via binding to hydroxyapatite. Once in the osteoclast, the <scene name='Sandbox_59/Active_site_ligand_space_fill/2'>alendronate binds</scene> to the active site of FPPS.<ref>Fisher et. all. ''Alendronate mechanism of action: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro''.Cell Biology, Vol. 96, pp. 133–138, January 1999</ref> In the active site, it appears that the alendronate interacts directly with <scene name='Sandbox_59/Active_site_ligand/2'>three Asp residues</scene>, not allowing the IPP to bind, and effectively daectivating FPPS.

The deactivation of FPPS causes a disruption of prenylation in the cell and thus affects various GTPases. For instance, it will incorrectly activate the GTPases Rho, Rac, and Cdc42.<ref>http://www.ncbi.nlm.nih.gov/pubmed/16734383</ref> The inhibition of post-translational prenylation of Ras is likely to cause cell apoptosis. <ref>http://www.ncbi.nlm.nih.gov/pubmed/9556058</ref>

==== FPPS Substrate ====

[[Image:IPP.png]]<ref>Image from: http://reference.findtarget.com</ref>

Isopentenyl pyrophosphate (IPP) actually binds to and stabilizes the alendronate-FPPS complex, rather than competing with the inhibitor.

== Side affects of Drug ==

== References ==

<references/>

Alendronate

2011-03-11T11:39:13Z

Anne Goodling:

{{Template:Oberholser_Sandbox_Reservation}}


== '''Alendronate (Fosamax®)''' ==

Alendronate is commonly known for its use in treatment and prevention of osteoporosis in postmenopausal women and men, but is also used to treat Paget's disease (disease that results in deformed and enlarged bones).<ref>http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000018/</ref> Alendronate belongs to the class of nitrogen-containing bisphosphonates, which are inorganic pyrophosphate analogues.

== History of Bisphosphonates ==

Bisphosphonates were first synthesized in Germany in 1865, but were not studied biologically until 1968. In the interim time, they were used in the textile and fertilizer industries due to their apparent inhibitory effect on calcium carbonate. However, in 1968, a group in Switzerland found inorganic pyrophosphates in urine and plasma. In vitro testing of these molecules revealed that they inhibited calcium phosphate precipitation and dissolution, but were destroyed in vivo by phosphatases. These results led to the discovery of bisphosphonates, as they reacted in the prescribed manner.<ref>http://www.ncbi.nlm.nih.gov/pmc/articles/PMC138713/?tool=pmcentrez</ref>

Sodium alendronate was first marketed in 1994 as Fosamax® by Merck pharmaceutical. In 2008, Merck lost their U.S. patent on alendronate, allowing Barr Pharmaceuticals and Teva Pharmaceuticals USA to begin marketing generic forms of sodium alendronate. Other brand names for the drug include Fosamax+D®, Adronat, Alendros, Arendal, and Onclast.<ref>http://www.drugbank.ca/drugs/DB00630</ref>

== Structure and General Function ==
[[Image:Alendronate.gif]]<ref>Image from: http://pharmacy-and-drugs.com</ref>

Alendronate is an aminobisphosphonate with a nonhydrolyzable P-C-P. Alendronate generally affects the activity of osteoclasts in bone. Osteoclasts are responsible for breaking down bone and also for bone resorption (losing bone substance). <ref>http://www.medterms.com/script/main/art.asp?articlekey=11794</ref> When alendronate is present, bone resorption is inhibited and bone breakdown is diminished.

== Target Proteins and Bone ==

Alendronate not only targets several proteins, but also directly binds to a bone mineral (hydroxyapatite), which causes the inhibition of bone resorption. The alendronate is bound to hydroxypatite and taken up into the osteoclsat during bone resorption.<ref>http://www.ncbi.nlm.nih.gov/pubmed/20209564</ref><ref>http://www.ncbi.nlm.nih.gov/pubmed/16046206</ref>

=== Protein-Tyrosine-Phosphatases (PTP) ===

Protein-Tyrosine-Phosphatses (PTPs) are reported to have an effect on osteoclast formation and function.<ref>
<scene name='Sandbox_59/Ptpre/1'>TextToBeDisplayed</scene></ref> Initial reports indicated that alendronate inhibited several types of PTPs, though specific mechanisms are not known. The data does suggest that alendronate works as an antagonist, which means that, when bound, the alendronate does not elicit a response from the protein but rather disallows the binding of an agonist which would cause a change (likely activating) in the protein.<ref>http://www.drugbank.ca/drugs/DB00630</ref><ref>http://www.ncbi.nlm.nih.gov/pubmed/8610169</ref><ref>http://www.ncbi.nlm.nih.gov/pubmed/9310349</ref> A
<scene name='Sandbox_59/Ptpre/1'>PTP example</scene> is given, so the binding site can be seen.

=== Farnesyl Pyrophosphate Synthase (FPPS) ===
<Structure load='2f92' size='450' frame='true' align='right' caption='Shown: The asymmetric subunit of FPPS, not the assumed biological molecule.' scene='Insert optional scene name here' />

<scene name='Sandbox_59/Fpps/3'>Farnesyl pyrophosphate synthase (FPPS)</scene> is considered the main target protein of aminobisphosphonates (including alendronate). FPPS is the prenyl transferase in the HMG-CoA Reductase Pathway, which forms cholesterol (sterols and terpenoids) from acetyl CoA. It reacts with 3-isopentenyl pyrophosphate (IPP) to form geranyl pyrophosphate (GGP). Researchers discovered that alendronate inhibits FPPS because they found a build-up of IPP in the cell, but less GGP.<ref>http://www.ncbi.nlm.nih.gov/pubmed/10620343</ref>

The identified mechanism of alendronate on FPPS begins with the absorption of the alendronate into the osteoclast via binding to hydroxyapatite. Once in the osteoclast, the <scene name='Sandbox_59/Active_site_ligand_space_fill/2'>alendronate binds</scene> to the active site of FPPS.<ref>Fisher et. all. ''Alendronate mechanism of action: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro''.Cell Biology, Vol. 96, pp. 133–138, January 1999</ref> In the active site, it appears that the alendronate interacts directly with <scene name='Sandbox_59/Active_site_ligand/2'>three Asp residues</scene>, not allowing the IPP to bind, and effectively daectivating FPPS.

The deactivation of FPPS causes a disruption of prenylation in the cell and thus affects various GTPases. For instance, it will incorrectly activate the GTPases Rho, Rac, and Cdc42.<ref>http://www.ncbi.nlm.nih.gov/pubmed/16734383</ref> The inhibition of post-translational prenylation of Ras is likely to cause cell apoptosis. <ref>http://www.ncbi.nlm.nih.gov/pubmed/9556058</ref>

==== FPPS Natural Substrates ====

[[Image:IPP.png]]<ref>Image from: http://reference.findtarget.com</ref>

Isopentenyl pyrophosphate (IPP) actually binds to and stabilizes the alendronate-FPPS complex, rather than competing with the inhibitor.

== Side affects of Drug ==

== References ==

<references/>

Alendronate

2011-03-11T11:28:58Z

Anne Goodling:

{{Template:Oberholser_Sandbox_Reservation}}


== '''Alendronate (Fosamax®)''' ==

Alendronate is commonly known for its use in treatment and prevention of osteoporosis in postmenopausal women and men, but is also used to treat Paget's disease (disease that results in deformed and enlarged bones).<ref>http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000018/</ref> Alendronate belongs to the class of nitrogen-containing bisphosphonates, which are inorganic pyrophosphate analogues.

== History of Bisphosphonates ==

Bisphosphonates were first synthesized in Germany in 1865, but were not studied biologically until 1968. In the interim time, they were used in the textile and fertilizer industries due to their apparent inhibitory effect on calcium carbonate. However, in 1968, a group in Switzerland found inorganic pyrophosphates in urine and plasma. In vitro testing of these molecules revealed that they inhibited calcium phosphate precipitation and dissolution, but were destroyed in vivo by phosphatases. These results led to the discovery of bisphosphonates, as they reacted in the prescribed manner.<ref>http://www.ncbi.nlm.nih.gov/pmc/articles/PMC138713/?tool=pmcentrez</ref>

Sodium alendronate was first marketed in 1994 as Fosamax® by Merck pharmaceutical. In 2008, Merck lost their U.S. patent on alendronate, allowing Barr Pharmaceuticals and Teva Pharmaceuticals USA to begin marketing generic forms of sodium alendronate. Other brand names for the drug include Fosamax+D®, Adronat, Alendros, Arendal, and Onclast.<ref>http://www.drugbank.ca/drugs/DB00630</ref>

== Structure and General Function ==
[[Image:Alendronate.gif]]<ref>Image from: http://pharmacy-and-drugs.com</ref>

Alendronate is an aminobisphosphonate with a nonhydrolyzable P-C-P. Alendronate generally affects the activity of osteoclasts in bone. Osteoclasts are responsible for breaking down bone and also for bone resorption (losing bone substance). <ref>http://www.medterms.com/script/main/art.asp?articlekey=11794</ref> When alendronate is present, bone resorption is inhibited and bone breakdown is diminished.

== Target Proteins and Bone ==

Alendronate not only targets several proteins, but also directly binds to a bone mineral (hydroxyapatite), which causes the inhibition of bone resorption. The alendronate is bound to hydroxypatite and taken up into the osteoclsat during bone resorption.<ref>http://www.ncbi.nlm.nih.gov/pubmed/20209564</ref><ref>http://www.ncbi.nlm.nih.gov/pubmed/16046206</ref>

=== Protein-Tyrosine-Phosphatases (PTP) ===

Protein-Tyrosine-Phosphatses (PTPs) are reported to have an effect on osteoclast formation and function.<ref>
<scene name='Sandbox_59/Ptpre/1'>TextToBeDisplayed</scene></ref> Initial reports indicated that alendronate inhibited several types of PTPs, though specific mechanisms are not known. The data does suggest that alendronate works as an antagonist, which means that, when bound, the alendronate does not elicit a response from the protein but rather disallows the binding of an agonist which would cause a change (likely activating) in the protein.<ref>http://www.drugbank.ca/drugs/DB00630</ref><ref>http://www.ncbi.nlm.nih.gov/pubmed/8610169</ref><ref>http://www.ncbi.nlm.nih.gov/pubmed/9310349</ref> A
<scene name='Sandbox_59/Ptpre/1'>PTP example</scene> is given, so the binding site can be seen.

=== Farnesyl Pyrophosphate Synthase (FPPS) ===
<Structure load='2f92' size='450' frame='true' align='right' caption='Shown: The asymmetric subunit of FPPS, not the assumed biological molecule.' scene='Insert optional scene name here' />

<scene name='Sandbox_59/Fpps/2'>FPPS</scene> is considered the main target protein of aminobisphosphonates (including alendronate). FPPS is the prenyl transferase in the HMG-CoA Reductase Pathway, which forms cholesterol (sterols and terpenoids) from acetyl CoA. It reacts with 3-isopentenyl pyrophosphate (IPP) to form geranyl pyrophosphate (GGP). Researchers discovered that alendronate inhibits FPPS because they found a build-up of IPP in the cell, but less GGP.<ref>http://www.ncbi.nlm.nih.gov/pubmed/10620343</ref>

The identified mechanism of alendronate on FPPS begins with the absorption of the alendronate into the osteoclast via binding to hydroxyapatite. Once in the osteoclast, the <scene name='Sandbox_59/Active_site_ligand_space_fill/2'>alendronate binds</scene> to the active site of FPPS.<ref>Fisher et. all. ''Alendronate mechanism of action: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro''.Cell Biology, Vol. 96, pp. 133–138, January 1999</ref> In the active site, it appears that the alendronate interacts directly with <scene name='Sandbox_59/Active_site_ligand/2'>three Asp residues</scene>, not allowing the IPP to bind, and effectively daectivating FPPS.

The deactivation of FPPS causes a disruption of prenylation in the cell and thus affects various GTPases. For instance, it will incorrectly activate the GTPases Rho, Rac, and Cdc42.<ref>http://www.ncbi.nlm.nih.gov/pubmed/16734383</ref> The inhibition of post-translational prenylation of Ras is likely to cause cell apoptosis. <ref>http://www.ncbi.nlm.nih.gov/pubmed/9556058</ref>

==== FPPS Natural Substrates ====

[[Image:IPP.png]]<ref>Image from: http://reference.findtarget.com</ref>

Isopentenyl pyrophosphate (IPP) actually binds to and stabilizes the alendronate-FPPS complex, rather than competing with the inhibitor.

== Side affects of Drug ==

== References ==

<references/>

Alendronate

2011-03-11T10:28:31Z

Anne Goodling:

{{Template:Oberholser_Sandbox_Reservation}}


== '''Alendronate (Fosamax®)''' ==

Alendronate is commonly known for its use in treatment and prevention of osteoporosis in postmenopausal women and men, but is also used to treat Paget's disease (disease that results in deformed and enlarged bones).<ref>http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000018/</ref> Alendronate belongs to the class of nitrogen-containing bisphosphonates, which are inorganic pyrophosphate analogues.

== History of Bisphosphonates ==

Bisphosphonates were first synthesized in Germany in 1865, but were not studied biologically until 1968. In the interim time, they were used in the textile and fertilizer industries due to their apparent inhibitory effect on calcium carbonate. However, in 1968, a group in Switzerland found inorganic pyrophosphates in urine and plasma. In vitro testing of these molecules revealed that they inhibited calcium phosphate precipitation and dissolution, but were destroyed in vivo by phosphatases. These results led to the discovery of bisphosphonates, as they reacted in the prescribed manner.<ref>http://www.ncbi.nlm.nih.gov/pmc/articles/PMC138713/?tool=pmcentrez</ref>

Sodium alendronate was first marketed in 1994 as Fosamax® by Merck pharmaceutical. In 2008, Merck lost their U.S. patent on alendronate, allowing Barr Pharmaceuticals and Teva Pharmaceuticals USA to begin marketing generic forms of sodium alendronate. Other brand names for the drug include Fosamax+D®, Adronat, Alendros, Arendal, and Onclast.<ref>http://www.drugbank.ca/drugs/DB00630</ref>

== Structure and General Function ==
[[Image:Alendronate.gif]]<ref>Image from: http://pharmacy-and-drugs.com</ref>

Alendronate is an aminobisphosphonate with a nonhydrolyzable P-C-P. Alendronate generally affects the activity of osteoclasts in bone. Osteoclasts are responsible for breaking down bone and also for bone resorption (losing bone substance). <ref>http://www.medterms.com/script/main/art.asp?articlekey=11794</ref> When alendronate is present, bone resorption is inhibited and bone breakdown is diminished.

== Target Proteins and Bone ==

Alendronate not only targets several proteins, but also directly binds to a bone mineral (hydroxyapatite), which causes the inhibition of bone resorption. The mechanism for this has not been elucidated.<ref>http://www.ncbi.nlm.nih.gov/pubmed/20209564</ref><ref>http://www.ncbi.nlm.nih.gov/pubmed/16046206</ref>

=== Protein-Tyrosine-Phosphatases (PTP) ===

Protein-Tyrosine-Phosphatses (PTPs) are reported to have an effect on osteoclast formation and function.<ref>
<scene name='Sandbox_59/Ptpre/1'>TextToBeDisplayed</scene></ref> Initial reports indicated that alendronate inhibited several types of PTPs, though specific mechanisms are not known. The data does suggest that alendronate works as an antagonist, which means that, when bound, the alendronate does not elicit a response from the protein but rather disallows the binding of an agonist which would cause a change (likely activating) in the protein.<ref>http://www.drugbank.ca/drugs/DB00630</ref><ref>http://www.ncbi.nlm.nih.gov/pubmed/8610169</ref><ref>http://www.ncbi.nlm.nih.gov/pubmed/9310349</ref> A
<scene name='Sandbox_59/Ptpre/1'>PTP example</scene> is given, so the binding site can be seen.

=== Farnesyl Pyrophosphate Synthase (FPPS) ===
<Structure load='2f92' size='450' frame='true' align='right' caption='Shown: The asymmetric subunit of FPPS, not the assumed biological molecule.' scene='Insert optional scene name here' />

<scene name='Sandbox_59/Fpps/2'>FPPS</scene> is considered the main target protein of aminobisphosphonates (including alendronate). FPPS is the prenyl transferase in the HMG-CoA Reductase Pathway, which forms cholesterol (sterols and terpenoids) from acetyl CoA. It reacts with 3-isopentenyl pyrophosphate.
The identified mechanism of alendronate on FPPS begins with the absorption of the alendronate into the osteoclast. Once in the osteoclast, the <scene name='Sandbox_59/Active_site_ligand_space_fill/2'>alendronate binds</scene> to the active site of FPPS.<ref>Fisher et. all. ''Alendronate mechanism of action: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro''.Cell Biology, Vol. 96, pp. 133–138, January 1999</ref>

<scene name='Sandbox_59/Active_site_ligand_space_fill/2'>alendronate binds</scene>
<scene name='Sandbox_59/Active_site_ligand/2'>active site bound sticks</scene>
<scene name='Sandbox_59/Fpps_bound_phosphate/2'>FPPS bound phosphate</scene>

==== FPPS Natural Substrates ====

[[Image:IPP.png]]<ref>Image from: http://reference.findtarget.com</ref>

Isopentenyl pyrophosphate (IPP) actually binds to and stabilizes the alendronate-FPPS complex, rather than competing with the inhibitor.

== Side affects of Drug ==

== References ==

<references/>

Alendronate

2011-03-11T10:02:39Z

Anne Goodling:

Alendronate

2011-03-11T09:52:22Z

Anne Goodling:

Alendronate

2011-03-11T08:18:38Z

Anne Goodling:

Alendronate

2011-03-11T08:15:44Z

Anne Goodling:

Alendronate

2011-03-11T06:50:05Z

Anne Goodling:

Alendronate

2011-03-11T06:43:35Z

Anne Goodling:

Alendronate

2011-03-11T06:41:54Z

Anne Goodling:

File:Alendronate.gif

2011-03-11T06:41:22Z

Anne Goodling:

Alendronate

2011-03-11T06:37:36Z

Anne Goodling:

File:IPP.png

2011-03-11T06:37:23Z

Anne Goodling: uploaded a new version of "Image:IPP.png"

Alendronate

2011-03-11T06:33:59Z

Anne Goodling:

Alendronate

2011-03-11T06:30:47Z

Anne Goodling:

File:IPP.png

2011-03-11T06:29:45Z

Anne Goodling:

Alendronate

2011-03-11T06:25:13Z

Anne Goodling: