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[[Image:1i2w.jpg|left|200px]]
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{{STRUCTURE_1i2w|  PDB=1i2w  |  SCENE=  }}
'''BETA-LACTAMASE FROM BACILLUS LICHENIFORMIS BS3 COMPLEXED WITH CEFOXITIN'''


==BETA-LACTAMASE FROM BACILLUS LICHENIFORMIS BS3 COMPLEXED WITH CEFOXITIN==
<StructureSection load='1i2w' size='340' side='right'caption='[[1i2w]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1i2w]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_licheniformis Bacillus licheniformis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1I2W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1I2W FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1QL:(2R)-5-[(carbamoyloxy)methyl]-2-{(1S)-1-methoxy-2-oxo-1-[(thiophen-2-ylacetyl)amino]ethyl}-3,6-dihydro-2H-1,3-thiazine-4-carboxylic+acid'>1QL</scene>, <scene name='pdbligand=OUT:CARBAMIC+ACID'>OUT</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1i2w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1i2w OCA], [https://pdbe.org/1i2w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1i2w RCSB], [https://www.ebi.ac.uk/pdbsum/1i2w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1i2w ProSAT]</span></td></tr>
</table>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i2/1i2w_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1i2w ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The Bacillus licheniformis BS3 beta-lactamase catalyzes the hydrolysis of the beta-lactam ring of penicillins, cephalosporins, and related compounds. The production of beta-lactamases is the most common and thoroughly studied cause of antibiotic resistance. Although they escape the hydrolytic activity of the prototypical Staphylococcus aureus beta-lactamase, many cephems are good substrates for a large number of beta-lactamases. However, the introduction of a 7alpha-methoxy substituent, as in cefoxitin, extends their antibacterial spectrum to many cephalosporin-resistant Gram-negative bacteria. The 7alpha-methoxy group selectively reduces the hydrolytic action of many beta-lactamases without having a significant effect on the affinity for the target enzymes, the membrane penicillin-binding proteins. We report here the crystallographic structures of the BS3 enzyme and its acyl-enzyme adduct with cefoxitin at 1.7 A resolution. The comparison of the two structures reveals a covalent acyl-enzyme adduct with perturbed active site geometry, involving a different conformation of the omega-loop that bears the essential catalytic Glu166 residue. This deformation is induced by the cefoxitin side chain whose position is constrained by the presence of the alpha-methoxy group. The hydrolytic water molecule is also removed from the active site by the 7beta-carbonyl of the acyl intermediate. In light of the interactions and steric hindrances in the active site of the structure of the BS3-cefoxitin acyl-enzyme adduct, the crucial role of the conserved Asn132 residue is confirmed and a better understanding of the kinetic results emerges.


==Overview==
Crystal structures of the Bacillus licheniformis BS3 class A beta-lactamase and of the acyl-enzyme adduct formed with cefoxitin.,Fonze E, Vanhove M, Dive G, Sauvage E, Frere JM, Charlier P Biochemistry. 2002 Feb 12;41(6):1877-85. PMID:11827533<ref>PMID:11827533</ref>
The Bacillus licheniformis BS3 beta-lactamase catalyzes the hydrolysis of the beta-lactam ring of penicillins, cephalosporins, and related compounds. The production of beta-lactamases is the most common and thoroughly studied cause of antibiotic resistance. Although they escape the hydrolytic activity of the prototypical Staphylococcus aureus beta-lactamase, many cephems are good substrates for a large number of beta-lactamases. However, the introduction of a 7alpha-methoxy substituent, as in cefoxitin, extends their antibacterial spectrum to many cephalosporin-resistant Gram-negative bacteria. The 7alpha-methoxy group selectively reduces the hydrolytic action of many beta-lactamases without having a significant effect on the affinity for the target enzymes, the membrane penicillin-binding proteins. We report here the crystallographic structures of the BS3 enzyme and its acyl-enzyme adduct with cefoxitin at 1.7 A resolution. The comparison of the two structures reveals a covalent acyl-enzyme adduct with perturbed active site geometry, involving a different conformation of the omega-loop that bears the essential catalytic Glu166 residue. This deformation is induced by the cefoxitin side chain whose position is constrained by the presence of the alpha-methoxy group. The hydrolytic water molecule is also removed from the active site by the 7beta-carbonyl of the acyl intermediate. In light of the interactions and steric hindrances in the active site of the structure of the BS3-cefoxitin acyl-enzyme adduct, the crucial role of the conserved Asn132 residue is confirmed and a better understanding of the kinetic results emerges.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1I2W is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Bacillus_licheniformis Bacillus licheniformis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1I2W OCA].
</div>
<div class="pdbe-citations 1i2w" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Crystal structures of the Bacillus licheniformis BS3 class A beta-lactamase and of the acyl-enzyme adduct formed with cefoxitin., Fonze E, Vanhove M, Dive G, Sauvage E, Frere JM, Charlier P, Biochemistry. 2002 Feb 12;41(6):1877-85. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11827533 11827533]
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bacillus licheniformis]]
[[Category: Bacillus licheniformis]]
[[Category: Beta-lactamase]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Charlier P]]
[[Category: Charlier, P.]]
[[Category: Dive G]]
[[Category: Dive, G.]]
[[Category: Fonze E]]
[[Category: Fonze, E.]]
[[Category: Frere JM]]
[[Category: Frere, J M.]]
[[Category: Sauvage E]]
[[Category: Sauvage, E.]]
[[Category: Vanhove M]]
[[Category: Vanhove, M.]]
[[Category: Antibiotic resistance]]
[[Category: Hydrolase]]
[[Category: Serine beta-lactamase]]
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Retrieved from "https://proteopedia.org/1i2w"