View source for 5zft


==Crystal structure of beta-lactamase PenP mutant-E166Y in complex with cephaloridine as "pre-deacylation" intermediate==
<StructureSection load='5zft' size='340' side='right'caption='[[5zft]], [[Resolution|resolution]] 1.93&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5zft]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"clostridium_licheniforme"_weigmann_1898 "clostridium licheniforme" weigmann 1898]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZFT OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5ZFT FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CED:5-METHYL-2-[2-OXO-1-(2-THIOPHEN-2-YL-ACETYLAMINO)-ETHYL]-3,6-DIHYDRO-2H-[1,3]THIAZINE-4-CARBOXYLIC+ACID'>CED</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">penP, blaP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1402 "Clostridium licheniforme" Weigmann 1898])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5zft FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zft OCA], [http://pdbe.org/5zft PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zft RCSB], [http://www.ebi.ac.uk/pdbsum/5zft PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zft ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Serine-based beta-lactamases of Class A, C and D all rely on a key water molecule to hydrolyze and inactivate beta-lactam antibiotics. This process involves two conserved catalytic steps. In the first acylation step, the beta-lactam antibiotic forms an acyl-enzyme intermediate (ES*) with the catalytic serine residue. In the second deacylation step, an activated water molecule serves as nucleophile (WAT_Nu) to attack ES* and release the inactivated beta-lactam. The coordination and activation of WAT_Nu is not fully understood. Using time-resolved x-ray crystallography and QM/MM simulations, we analyzed three intermediate structures of Class A beta-lactamase PenP as it slowly hydrolyzed cephaloridine. WAT_Nu is centrally located in the apo structure but becomes slightly displaced away by ES* in the post-acylation structure. In the deacylation structure, WAT_Nu moves back and is positioned along the Burgi-Dunitz trajectory with favorable energetic profile to attack ES*. Unexpectedly, WAT_Nu is also found to adopt a catalytically incompetent conformation in the deacylation structure forming a hydrogen bond with ES*. Our results reveal that ES* plays a significant role in coordinating and activating WAT_Nu through subtle yet distinct interactions at different stages of the catalytic process. These interactions may serve as potential targets to circumvent beta-lactamase-mediated antibiotic resistance.

The hydrolytic water molecule of Class A beta-lactamase relies on the acyl-enzyme intermediate ES* for proper coordination and catalysis.,He Y, Lei J, Pan X, Huang X, Zhao Y Sci Rep. 2020 Jun 23;10(1):10205. doi: 10.1038/s41598-020-66431-w. PMID:32576842<ref>PMID:32576842</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5zft" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Clostridium licheniforme weigmann 1898]]
[[Category: Beta-lactamase]]
[[Category: Large Structures]]
[[Category: Pan, X]]
[[Category: Zhao, Y]]
[[Category: Antibiotic resistance]]
[[Category: Class a beta-lactamase]]
[[Category: Hydrolase]]