Proteopedia - User contributions [en]

User:Michael Patrick/Sandbox 3

2011-04-26T14:44:37Z

Michael Patrick: New page: triall....cholera toxin

triall....cholera toxin

User:Michael Patrick/Sandbox 2

2011-04-09T16:25:47Z

Michael Patrick:

=='''GREEN FLUORESCENT PROTEIN'''==
----
===INTRODUCTION===
[[Image:1EMA(GFP).jpg|300px|left|thumb|Green Fluorescent Protein,[[1ema]]]] [[Image:Aquaria victoria.jpg|300px|right|thumb|''Aquorea victoria'']]
The '''green fluorescent protein''' (GFP) is a protein composed of 238 amino acid residues (26.9kDa) that exhibits bright green fluorescence when exposed to blue light. Although many other marine organisms have similar green fluorescent proteins, GFP traditionally refers to the protein first isolated from the jellyfish ''Aequorea victoria''. The GFP from ''A. victoria'' has a major excitation peak at a wavelength of 395 nm and a minor one at 475 nm. Its emission peak is at 509 nm, which is in the lower green portion of the visible spectrum. The GFP from the sea pansy (''Renilla reniformis'') has a single major excitation peak at 498 nm. In cell and molecular biology, the GFP gene is frequently used as a reporter of expression. In modified forms it has been used to make biosensors, and many animals have been created that express GFP as a proof-of-concept that a gene can be expressed throughout a given organism. The GFP gene can be introduced into organisms and maintained in their genome through breeding, injection with a viral vector, or cell transformation. To date, the GFP gene has been introduced and expressed in many bacteria, yeast and other fungi, fish (such as zebrafish), plant, fly, and mammalian cells, including human. Martin Chalfie, Osamu Shimomura, and Roger Y. Tsien were awarded the 2008 Nobel Prize in Chemistry on 10 October 2008 for their discovery and development of the green fluorescent protein.
----
===HISTORY===
In the 1960s and 1970s, GFP, along with the separate luminescent protein [[aequorin]], was first purified from ''Aequorea victoria'' and its properties studied by Osamu Shimomura.[1] In ''A. victoria'', GFP fluorescence occurs when aequorin interacts with Ca2+ ions, inducing a blue glow. Some of this luminescent energy is transferred to the GFP, shifting the overall color towards green.[2] However, its utility as a tool for molecular biologists did not begin to be realized until 1992 when Douglas Prasher reported the cloning and nucleotide sequence of wtGFP in Gene.[3] The funding for this project had run out, so Prasher sent cDNA samples to several labs. The lab of Martin Chalfie expressed the coding sequence of wtGFP, with the first few amino acids deleted, in heterologous cells of E. coli and C. elegans, publishing the results in Science in 1994.[4] Frederick Tsuji's lab independently reported the expression of the recombinant protein one month later.[5] Remarkably, the GFP molecule folded and was fluorescent at room temperature, without the need for exogenous cofactors specific to the jellyfish. Although this near-wtGFP was fluorescent, it had several drawbacks, including dual peaked excitation spectra, pH sensitivity, chloride sensitivity, poor fluorescence quantum yield, poor photostability and poor folding at 37°C.

The first reported crystal structure of a GFP was that of the S65T mutant by the Remington group in Science in 1996.[5] One month later, the Phillips group independently reported the wild-type GFP structure in Nature Biotech.[9] These crystal structures provided vital background on chromophore formation and neighboring residue interactions. Researchers have modified these residues by directed and random mutagenesis to produce the wide variety of GFP derivatives in use today.
----
===GFP DERIVATIVES===
[[Image:GFP derivatives.jpg|300px|left|thumb|The diversity of genetic mutations is illustrated by this San Diego beach scene drawn with living bacteria expressing 8 different colors of fluorescent proteins.]]
Due to the potential for widespread usage and the evolving needs of researchers, many different mutants of GFP have been engineered. The first major improvement was a single point mutation (S65T) reported in 1995 in Nature by Roger Tsien[10]. This mutation dramatically improved the spectral characteristics of GFP, resulting in increased fluorescence, photostability, and a shift of the major excitation peak to 488 nm, with the peak emission kept at 509 nm. This matched the spectral characteristics of commonly available [[FITC filter sets]], increasing the practicality of use by the general researcher. A 37 °C folding efficiency (F64L) point mutant to this scaffold yielding enhanced GFP (EGFP) was discovered in 1995 by the lab of Ole Thastrup[11] EGFP allowed the practical use of GFPs in mammalian cells. EGFP has an [[extinction coefficient]] (denoted ε) of 55,000 M−1cm−1. The [[fluorescence quantum yield]] (QY) of EGFP is 0.60. The relative brightness, expressed as ε•QY, is 33,000 M−1cm−1. Superfolder GFP, a series of mutations that allow GFP to rapidly fold and mature even when fused to poorly folding peptides, was reported in 2006[12]
Many other mutations have been made, including color mutants; in particular, blue fluorescent protein (EBFP, EBFP2, Azurite, mKalama1), cyan fluorescent protein (ECFP, Cerulean, CyPet), and yellow fluorescent protein derivatives (YFP, Citrine, Venus, YPet). BFP derivatives (except mKalama1) contain the Y66H substitution. The critical mutation in cyan derivatives is the Y66W substitution, which causes the chromophore to form with an indole rather than phenol component. Several additional compensatory mutations in the surrounding barrel are required to restore brightness to this modified chromophore due to the increased bulk of the indole group. The red-shifted wavelength of the YFP derivatives is accomplished by the T203Y mutation and is due to π-electron stacking interactions between the substituted tyrosine residue and the chromophore. These two classes of spectral variants are often employed for [[fluorescence resonance energy transfer]] (FRET) experiments. Genetically-encoded FRET reporters sensitive to cell signaling molecules, such as calcium or glutamate, protein phosphorylation state, protein complementation, receptor dimerization, and other processes provide highly specific optical readouts of cell activity in real time.

Semirational mutagenesis of a number of residues led to pH-sensitive mutants known as pHluorins, and later super-ecliptic pHluorins[13]. By exploiting the rapid change in pH upon synaptic vesicle fusion, pHluorins tagged to synaptobrevin have been used to visualize synaptic activity in neurons

Redox sensitive versions of GFP (roGFP) were engineered by introduction of cysteines into the beta barrel structure[14]. The redox state of the cysteines determines the fluorescent properties of roGFP
The nomenclature of modified GFPs is often confusing due to overlapping mapping of several GFP versions onto a single name. For example, mGFP often refers to a GFP with an N-terminal palmitoylation that causes the GFP to bind to cell membranes. However, the same term is also used to refer to monomeric GFP, which is often achieved by the dimer interface breaking A206K mutation.[15] Wild-type GFP has a weak dimerization tendency at concentrations above 5 mg/mL. mGFP also stands for "modified GFP," which has been optimized through amino acid exchange for stable expression in plant cells.
----
===STRUCTURE===
<Structure load='1ema' size='500' frame='true' align='right' caption='GFP in backbone format and spacefill chromophore' scene='User:Michael_Patrick/Sandbox_2/Ema-1/2' />
GFP has a typical beta barrel consisting of <scene name='User:Michael_Patrick/Sandbox_2/Ema-3/4'>one β-sheet</scene> with <scene name='User:Michael_Patrick/Sandbox_2/Ema-3/3'>alpha helix(s) containing the chromophore running through the center.</scene> Inward-facing sidechains of the barrel induce specific cyclization reactions in the <scene name='User:Michael_Patrick/Sandbox_2/Ema-3/5'>tripeptide Ser65–Tyr66–Gly67</scene> that lead to chromophore formation. This process of post-translational modification is referred to as maturation. The hydrogen-bonding network and electron-stacking interactions with these sidechains influence the color of wtGFP and its numerous derivatives.
<scene name='User:Michael_Patrick/Sandbox_2/Ema-3/6'>The tightly packed nature of the barrel</scene> excludes solvent molecules, protecting the chromophore fluorescence from quenching by water.
----
===NOTES AND LITERATURE REFERENCES===

User:Michael Patrick/Sandbox 2

2011-04-08T20:26:33Z

Michael Patrick:

2011-04-07T21:24:53Z

Michael Patrick:

User:Michael Patrick/Sandbox 2

2011-04-07T20:08:12Z

Michael Patrick: New page: ==GREEN FLUORESCENT PROTEIN== ---- ===INTRODUCTION=== Green Fluorescent Protein,[[1emb]]

==GREEN FLUORESCENT PROTEIN==
----
===INTRODUCTION===
[[Image:1EMB(GFP).jpg|300px|left|thumb|Green Fluorescent Protein,[[1emb]]]]

File:GFP derivatives.jpg

2011-04-07T19:57:13Z

Michael Patrick:

2011-03-04T17:15:02Z

Michael Patrick: Removing all content from page

User:Michael Patrick

2011-03-04T16:09:49Z

Michael Patrick:

*Professor Emeritus, University of Wisconsin-Madison
*Academic Positions: Co-Director, Wisconsin Teacher Enhancement Program in Biology, University of Wisconsin-Madison
** Co-Director, Center for BioMolecular Modeling, Milwaukee School of Engineering
** Adjunct Professor of Chemistry and Physics, Milwaukee School of Engineering
** Professor of Molecular and Cell Biology, University of Texas at Dallas
*Education: Post doctoral fellow, Department of Biochemistry, Johns Hopkins University
** Ph.D. Biophysics, University of Chicago
** B.S. Biology and Chemistry, University of California, Santa Barbara

[[user:Michael Patrick/Sandbox 1]]
[[user:Michael Patrick/Sandbox 2]]

Sandbox Mati

2011-03-03T20:42:59Z

Michael Patrick:

=='''MYOGLOBIN'''==
----
[[ Image:1MBO_oxymyo-1.jpg|300px|left| | thumb| oxymyoglobin 1MBO]]
----
===Background===
----
'''Myoglobin''' is an iron- and oxygen-binding protein found in the muscle tissue of vertebrates in general and in almost all mammals. It is related to [[hemoglobin]], which is the iron- and oxygen-binding protein in blood, specifically in the red blood cells. The only time myoglobin is found in the bloodstream is when it is released following muscle injury. It is an abnormal finding, and can be diagnostically relevant when found in blood.

Myoglobin (abbreviated Mb) is a single-chain globular protein of 153 or 154 amino acids, containing a heme (iron-containing porphyrin) prosthetic group in the center around which the remaining apoprotein folds. It has eight alpha helices and a hydrophobic core. It has a molecular weight of 16,700 daltons, and is the primary oxygen-carrying pigment of muscle tissues. Unlike the blood-borne hemoglobin, to which it is structurally related, this protein does not exhibit cooperative binding of oxygen, since positive cooperativity is a property of multimeric/oligomeric proteins only. Instead, the binding of oxygen by myoglobin is unaffected by the oxygen pressure in the surrounding tissue. Myoglobin is often cited as having an "instant binding tenacity" to oxygen given its hyperbolic oxygen dissociation curve. High concentrations of myoglobin in muscle cells allow organisms to hold their breaths longer. Diving mammals such as whales and seals have muscles with particularly high myoglobin abundance.

Myoglobin was the first protein to have its three-dimensional structure revealed. In 1958, John Kendrew and associates successfully determined the structure of myoglobin by high-resolution[[ X-ray crystallography]]. For this discovery, John Kendrew shared the 1962 Nobel Prize in chemistry with Max Perutz. Despite being one of the most studied proteins in biology, its true physiological function is not yet conclusively established: mice genetically engineered to lack myoglobin are viable, but showed a 30% reduction in cardiac systolic output. They adapted to this deficiency through hypoxic genetic mechanisms and increased vasodilation. In humans myoglobin is encoded by the MB gene.
----
===PDB Entry===
1MBO is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Physeter_catodon Physeter catodon]. The January 2000 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Myoglobin'' by David S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2000_1 10.2210/rcsb_pdb/mom_2000_1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MBO OCA].
----

===About This Structure===
----
<Structure load='1mbo' size='500' frame='true' align='right' caption='oxymyoglobin ([[1mbo]])' scene='Insert optional scene name here' />

This is a cartoon representation of the myoglobin molecule. Not shown are the layers of water bound to its surface. This water is strongly attracted to the protein and is part of the structure of any crystalline protein. Hiding the water reveals that the overall tertiary shape is much like a hockey puck. The α-helix is a prominent secondary structural component. <scene name='Sandbox/Alpha_helices/1'>The α-helices can be shown to form two layers of backbone</scene>, and myoglobin can be classified as an antiparallel α-helix type of globular protein. The [[Myoglobin]] page gives more detail on the secondary structure. The Ramachandran plot shows most of the residues involved in an α-helix are clustered in the area of the plot where one would expect them to be. (Review Ramachandran Plot.) Many of the residues that are outside of the expected cluster are at the end of a helix, and it is not unusual for such residues to have ψ and φ values that are outside of the range for the α-helix. Also notice that many of the residues that are in the quadrants on the right are Gly. (Residues can be identified by hovering over the sphere with the cursor.) <scene name='Sandbox/Prosthetic_group/1'>The prosthetic group of myoglobin is a heme</scene>, and as shown here it is inserted into a pocket which is nonpolar. Empty heme pocket lined with translucent surface shows that except for some oxygen on the bottom and His 93 at the mid point of one side the pocket is lined with nonpolar carbon atoms. The mostly nonpolar heme inserts into this pocket with the two carboxylate groups of the heme being on the molecular surface. Detailed description of heme structure. The heme shown in the pocket with the pocket's surface colored white so that the heme can be distinguished from the protein surface atoms. His 93 is the fifth ligand chelated to Fe2+ (the other four are the nitrogens in the pyrole rings), and it binds to one side of the heme. Show protein atoms displayed as spacefill that are within 0.5 nm of the heme. These are the atoms which form the surface of the heme pocket and serve as a reminder that except for the ones on the surface of the molecule most of these atoms are carbon atoms and produce a nonpolar environment for the heme. This nonpolar, water-excluding environment is important for the function of myoglobin. Whenever Fe2+ is in an aqueous environment and it contacts O2, Fe2+ is oxidized to Fe3+. Myoglobin with a heme containing Fe3+ (called metmyoglobin) can not fulfill its physiological function and therefore must be degraded

----
===Role in Disease===
----
Myoglobin is released from damaged muscle tissue (rhabdomyolysis), which has very high concentrations of myoglobin. The released myoglobin is filtered by the kidneys but is toxic to the renal tubular epithelium and so may cause acute renal failure.

Myoglobin is a sensitive marker for muscle injury, making it a potential marker for heart attack in patients with chest pain. However, elevated myoglobin has low specificity for acute myocardial infarction (AMI) and thus CK-MB, cTnT, ECG, and clinical signs should be taken into account to make the diagnosis.
----
===Reference for the Structure===
<ref group="xtra">PMID:7463482</ref><references group="xtra"/>
[[Category: Myoglobin]]
[[Category: Physeter catodon]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: Phillips, S E.V.]]
[[Category: Oxygen storage]]
----
===Notes and Literature References===
----
===See Also===
----
===Additional Literature and Resources===
----

Sandbox Mati

2011-03-03T20:35:56Z

Michael Patrick:

=='''MYOGLOBIN'''==
----
[[ Image:1MBO_oxymyo-1.jpg|300px|left| | thumb| oxymyoglobin 1MBO]]
----
===Background===
----
'''Myoglobin''' is an iron- and oxygen-binding protein found in the muscle tissue of vertebrates in general and in almost all mammals. It is related to [[hemoglobin]], which is the iron- and oxygen-binding protein in blood, specifically in the red blood cells. The only time myoglobin is found in the bloodstream is when it is released following muscle injury. It is an abnormal finding, and can be diagnostically relevant when found in blood.

Myoglobin (abbreviated Mb) is a single-chain globular protein of 153 or 154 amino acids, containing a heme (iron-containing porphyrin) prosthetic group in the center around which the remaining apoprotein folds. It has eight alpha helices and a hydrophobic core. It has a molecular weight of 16,700 daltons, and is the primary oxygen-carrying pigment of muscle tissues. Unlike the blood-borne hemoglobin, to which it is structurally related, this protein does not exhibit cooperative binding of oxygen, since positive cooperativity is a property of multimeric/oligomeric proteins only. Instead, the binding of oxygen by myoglobin is unaffected by the oxygen pressure in the surrounding tissue. Myoglobin is often cited as having an "instant binding tenacity" to oxygen given its hyperbolic oxygen dissociation curve. High concentrations of myoglobin in muscle cells allow organisms to hold their breaths longer. Diving mammals such as whales and seals have muscles with particularly high myoglobin abundance.

Myoglobin was the first protein to have its three-dimensional structure revealed. In 1958, John Kendrew and associates successfully determined the structure of myoglobin by high-resolution[[ X-ray crystallography]]. For this discovery, John Kendrew shared the 1962 Nobel Prize in chemistry with Max Perutz. Despite being one of the most studied proteins in biology, its true physiological function is not yet conclusively established: mice genetically engineered to lack myoglobin are viable, but showed a 30% reduction in cardiac systolic output. They adapted to this deficiency through hypoxic genetic mechanisms and increased vasodilation. In humans myoglobin is encoded by the MB gene.
----
===PDB Entry===
1MBO is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Physeter_catodon Physeter catodon]. The January 2000 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Myoglobin'' by David S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2000_1 10.2210/rcsb_pdb/mom_2000_1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MBO OCA].
----

===About This Structure===
----
<Structure load='1mbo' size='500' frame='true' align='right' caption='oxymyoglobin ([[1mbo]])' scene='Insert optional scene name here' />

This is a cartoon representation of the myoglobin molecule. Not shown are the layers of water bound to its surface. This water is strongly attracted to the protein and is part of the structure of any crystalline protein. Hiding the water reveals that the overall tertiary shape is much like a hockey puck. The α-helix is a prominent secondary structural component. <scene name='Sandbox/Alpha_helices/1'>The α-helices can be shown to form two layers of backbone</scene>, and myoglobin can be classified as an antiparallel α-helix type of globular protein. The [[Myoglobin]] page gives more detail on the secondary structure. The Ramachandran plot shows most of the residues involved in an α-helix are clustered in the area of the plot where one would expect them to be. (Review Ramachandran Plot.) Many of the residues that are outside of the expected cluster are at the end of a helix, and it is not unusual for such residues to have ψ and φ values that are outside of the range for the α-helix. Also notice that many of the residues that are in the quadrants on the right are Gly. (Residues can be identified by hovering over the sphere with the cursor.) The prosthetic group of myoglobin is a heme, and as shown here it is inserted into a pocket which is nonpolar. Empty heme pocket lined with translucent surface shows that except for some oxygen on the bottom and His 93 at the mid point of one side the pocket is lined with nonpolar carbon atoms. The mostly nonpolar heme inserts into this pocket with the two carboxylate groups of the heme being on the molecular surface. Detailed description of heme structure. The heme shown in the pocket with the pocket's surface colored white so that the heme can be distinguished from the protein surface atoms. His 93 is the fifth ligand chelated to Fe2+ (the other four are the nitrogens in the pyrole rings), and it binds to one side of the heme. Show protein atoms displayed as spacefill that are within 0.5 nm of the heme. These are the atoms which form the surface of the heme pocket and serve as a reminder that except for the ones on the surface of the molecule most of these atoms are carbon atoms and produce a nonpolar environment for the heme. This nonpolar, water-excluding environment is important for the function of myoglobin. Whenever Fe2+ is in an aqueous environment and it contacts O2, Fe2+ is oxidized to Fe3+. Myoglobin with a heme containing Fe3+ (called metmyoglobin) can not fulfill its physiological function and therefore must be degraded

----
===Role in Disease===
----
Myoglobin is released from damaged muscle tissue (rhabdomyolysis), which has very high concentrations of myoglobin. The released myoglobin is filtered by the kidneys but is toxic to the renal tubular epithelium and so may cause acute renal failure.

Myoglobin is a sensitive marker for muscle injury, making it a potential marker for heart attack in patients with chest pain. However, elevated myoglobin has low specificity for acute myocardial infarction (AMI) and thus CK-MB, cTnT, ECG, and clinical signs should be taken into account to make the diagnosis.
----
===Reference for the Structure===
<ref group="xtra">PMID:7463482</ref><references group="xtra"/>
[[Category: Myoglobin]]
[[Category: Physeter catodon]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: Phillips, S E.V.]]
[[Category: Oxygen storage]]
----
===Notes and Literature References===
----
===See Also===
----
===Additional Literature and Resources===
----

Sandbox Mati

2011-03-03T19:25:48Z

Michael Patrick:

=='''MYOGLOBIN'''==
----
[[ Image:1MBO_oxymyo-1.jpg|300px|left| | thumb| oxymyoglobin 1MBO]]
----
===Background===
----
'''Myoglobin''' is an iron- and oxygen-binding protein found in the muscle tissue of vertebrates in general and in almost all mammals. It is related to [[hemoglobin]], which is the iron- and oxygen-binding protein in blood, specifically in the red blood cells. The only time myoglobin is found in the bloodstream is when it is released following muscle injury. It is an abnormal finding, and can be diagnostically relevant when found in blood.

Myoglobin (abbreviated Mb) is a single-chain globular protein of 153 or 154 amino acids, containing a heme (iron-containing porphyrin) prosthetic group in the center around which the remaining apoprotein folds. It has eight alpha helices and a hydrophobic core. It has a molecular weight of 16,700 daltons, and is the primary oxygen-carrying pigment of muscle tissues. Unlike the blood-borne hemoglobin, to which it is structurally related, this protein does not exhibit cooperative binding of oxygen, since positive cooperativity is a property of multimeric/oligomeric proteins only. Instead, the binding of oxygen by myoglobin is unaffected by the oxygen pressure in the surrounding tissue. Myoglobin is often cited as having an "instant binding tenacity" to oxygen given its hyperbolic oxygen dissociation curve. High concentrations of myoglobin in muscle cells allow organisms to hold their breaths longer. Diving mammals such as whales and seals have muscles with particularly high myoglobin abundance.

Myoglobin was the first protein to have its three-dimensional structure revealed. In 1958, John Kendrew and associates successfully determined the structure of myoglobin by high-resolution[[ X-ray crystallography]]. For this discovery, John Kendrew shared the 1962 Nobel Prize in chemistry with Max Perutz. Despite being one of the most studied proteins in biology, its true physiological function is not yet conclusively established: mice genetically engineered to lack myoglobin are viable, but showed a 30% reduction in cardiac systolic output. They adapted to this deficiency through hypoxic genetic mechanisms and increased vasodilation. In humans myoglobin is encoded by the MB gene.
----
===PDB Entry===
1MBO is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Physeter_catodon Physeter catodon]. The January 2000 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Myoglobin'' by David S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2000_1 10.2210/rcsb_pdb/mom_2000_1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MBO OCA].
----

===About This Structure===
----
<Structure load='1mbo' size='500' frame='true' align='right' caption='oxymyoglobin ([[1mbo]])' scene='Insert optional scene name here' />

This is a cartoon representation of the myoglobin molecule. Not shown are the layers of water bound to its surface. This water is strongly attracted to the protein and is part of the structure of any crystalline protein. Hiding the water reveals that the overall tertiary shape is much like a hockey puck. The α-helix is a prominent secondary structural component. The α-helices can be shown to form two layers of backbone, and myoglobin can be classified as an antiparallel α-helix type of globular protein. The [[Myoglobin]] page gives more detail on the secondary structure. The Ramachandran plot shows most of the residues involved in an α-helix are clustered in the area of the plot where one would expect them to be. (Review Ramachandran Plot.) Many of the residues that are outside of the expected cluster are at the end of a helix, and it is not unusual for such residues to have ψ and φ values that are outside of the range for the α-helix. Also notice that many of the residues that are in the quadrants on the right are Gly. (Residues can be identified by hovering over the sphere with the cursor.) The prosthetic group of myoglobin is a heme, and as shown here it is inserted into a pocket which is nonpolar. Empty heme pocket lined with translucent surface shows that except for some oxygen on the bottom and His 93 at the mid point of one side the pocket is lined with nonpolar carbon atoms. The mostly nonpolar heme inserts into this pocket with the two carboxylate groups of the heme being on the molecular surface. Detailed description of heme structure. The heme shown in the pocket with the pocket's surface colored white so that the heme can be distinguished from the protein surface atoms. His 93 is the fifth ligand chelated to Fe2+ (the other four are the nitrogens in the pyrole rings), and it binds to one side of the heme. Show protein atoms displayed as spacefill that are within 0.5 nm of the heme. These are the atoms which form the surface of the heme pocket and serve as a reminder that except for the ones on the surface of the molecule most of these atoms are carbon atoms and produce a nonpolar environment for the heme. This nonpolar, water-excluding environment is important for the function of myoglobin. Whenever Fe2+ is in an aqueous environment and it contacts O2, Fe2+ is oxidized to Fe3+. Myoglobin with a heme containing Fe3+ (called metmyoglobin) can not fulfill its physiological function and therefore must be degraded

----
===Role in Disease===
----
Myoglobin is released from damaged muscle tissue (rhabdomyolysis), which has very high concentrations of myoglobin. The released myoglobin is filtered by the kidneys but is toxic to the renal tubular epithelium and so may cause acute renal failure.

Myoglobin is a sensitive marker for muscle injury, making it a potential marker for heart attack in patients with chest pain. However, elevated myoglobin has low specificity for acute myocardial infarction (AMI) and thus CK-MB, cTnT, ECG, and clinical signs should be taken into account to make the diagnosis.
----
===Reference for the Structure===
<ref group="xtra">PMID:7463482</ref><references group="xtra"/>
[[Category: Myoglobin]]
[[Category: Physeter catodon]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: Phillips, S E.V.]]
[[Category: Oxygen storage]]
----
===Notes and Literature References===
----
===See Also===
----
===Additional Literature and Resources===
----

2011-03-02T21:16:15Z

Michael Patrick: backbone/heme/oxygen/spacefill 400

backbone/heme/oxygen/spacefill 400

Sandbox Mati

2011-03-02T20:35:35Z

Michael Patrick:

=='''MYOGLOBIN'''==
----
[[ Image:1MBO_oxymyo-1.jpg|300px|left| | thumb| oxymyoglobin 1MBO]]
----

===OVERVIEW===

'''Myoglobin''' is an iron- and oxygen-binding protein found in the muscle tissue of vertebrates in general and in almost all mammals. It is related to hemoglobin, which is the iron- and oxygen-binding protein in blood, specifically in the red blood cells. The only time myoglobin is found in the bloodstream is when it is released following muscle injury. It is an abnormal finding, and can be diagnostically relevant when found in blood.
Myoglobin (abbreviated Mb) is a single-chain globular protein of 153 or 154 amino acids, containing a heme (iron-containing porphyrin) prosthetic group in the center around which the remaining apoprotein folds. It has eight alpha helices and a hydrophobic core. It has a molecular weight of 16,700 daltons, and is the primary oxygen-carrying pigment of muscle tissues. Unlike the blood-borne hemoglobin, to which it is structurally related, this protein does not exhibit cooperative binding of oxygen, since positive cooperativity is a property of multimeric/oligomeric proteins only. Instead, the binding of oxygen by myoglobin is unaffected by the oxygen pressure in the surrounding tissue. Myoglobin is often cited as having an "instant binding tenacity" to oxygen given its hyperbolic oxygen dissociation curve. High concentrations of myoglobin in muscle cells allow organisms to hold their breaths longer. Diving mammals such as whales and seals have muscles with particularly high myoglobin abundance.

Myoglobin was the first protein to have its three-dimensional structure revealed. In 1958, John Kendrew and associates successfully determined the structure of myoglobin by high-resolution X-ray crystallography. For this discovery, John Kendrew shared the 1962 Nobel Prize in chemistry with Max Perutz. Despite being one of the most studied proteins in biology, its true physiological function is not yet conclusively established: mice genetically engineered to lack myoglobin are viable, but showed a 30% reduction in cardiac systolic output. They adapted to this deficiency through hypoxic genetic mechanisms and increased vasodilation. In humans myoglobin is encoded by the MB gene.

----
===STRUCTURE AND FUNCTION===

----
===PATHOLOGY===
Myoglobin is released from damaged muscle tissue (rhabdomyolysis), which has very high concentrations of myoglobin. The released myoglobin is filtered by the kidneys but is toxic to the renal tubular epithelium and so may cause acute renal failure.

Myoglobin is a sensitive marker for muscle injury, making it a potential marker for heart attack in patients with chest pain. However, elevated myoglobin has low specificity for acute myocardial infarction (AMI) and thus CK-MB, cTnT, ECG, and clinical signs should be taken into account to make the diagnosis.

----
===REFERENCES===

Replace the PDB id (use lowercase!) after the STRUCTURE_ and after PDB= to load
and display another structure.

{{STRUCTURE_3cin | PDB=3cin | SCENE= }}

Sandbox Mati

2011-03-02T19:53:40Z

Michael Patrick:

=='''MYOGLOBIN'''==
----
[[ Image:1MBO_oxymyo-1.jpg | thumb| oxymyoglobin 1MBO]]
----

===OVERVIEW===

'''Myoglobin''' is an iron- and oxygen-binding protein found in the muscle tissue of vertebrates in general and in almost all mammals. It is related to hemoglobin, which is the iron- and oxygen-binding protein in blood, specifically in the red blood cells. The only time myoglobin is found in the bloodstream is when it is released following muscle injury. It is an abnormal finding, and can be diagnostically relevant when found in blood.
Myoglobin (abbreviated Mb) is a single-chain globular protein of 153 or 154 amino acids, containing a heme (iron-containing porphyrin) prosthetic group in the center around which the remaining apoprotein folds. It has eight alpha helices and a hydrophobic core. It has a molecular weight of 16,700 daltons, and is the primary oxygen-carrying pigment of muscle tissues. Unlike the blood-borne hemoglobin, to which it is structurally related, this protein does not exhibit cooperative binding of oxygen, since positive cooperativity is a property of multimeric/oligomeric proteins only. Instead, the binding of oxygen by myoglobin is unaffected by the oxygen pressure in the surrounding tissue. Myoglobin is often cited as having an "instant binding tenacity" to oxygen given its hyperbolic oxygen dissociation curve. High concentrations of myoglobin in muscle cells allow organisms to hold their breaths longer. Diving mammals such as whales and seals have muscles with particularly high myoglobin abundance.
Myoglobin was the first protein to have its three-dimensional structure revealed. In 1958, John Kendrew and associates successfully determined the structure of myoglobin by high-resolution X-ray crystallography. For this discovery, John Kendrew shared the 1962 Nobel Prize in chemistry with Max Perutz. Despite being one of the most studied proteins in biology, its true physiological function is not yet conclusively established: mice genetically engineered to lack myoglobin are viable, but showed a 30% reduction in cardiac systolic output. They adapted to this deficiency through hypoxic genetic mechanisms and increased vasodilation. In humans myoglobin is encoded by the MB gene.

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===STRUCTURE AND FUNCTION===

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===PATHOLOGY===

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===REFERENCES===

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{{STRUCTURE_3cin | PDB=3cin | SCENE= }}

Sandbox Mati

2011-03-02T19:03:57Z

Michael Patrick:

=='''MYOGLOBIN'''==
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===OVERVIEW===
[[Image:1MBO_oxymyo-1.jpg]]
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===STRUCTURE AND FUNCTION===

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===PATHOLOGY===
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===REFERENCES===

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File:1MBO oxymyo-1.jpg

2011-03-02T18:34:53Z

Michael Patrick: This is a picture of 1mbo in cartoon format.

This is a picture of 1mbo in cartoon format.

Sandbox Mati

2011-03-02T15:26:16Z

Michael Patrick: Removing all content from page

Sandbox Mati

2011-02-16T20:26:31Z

Michael Patrick:

===Placeholder===

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Sandbox Mati

2011-02-16T15:02:14Z

Michael Patrick: add link to hemoglobin page

===MY NEW PAGE===
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'''Hello, this is my new page'''
Add a link to [[hemoglobin]]
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2011-02-02T18:20:37Z

Michael Patrick: