View source for 4gog


==Crystal structure of the GES-1 imipenem acyl-enzyme complex==
<StructureSection load='4gog' size='340' side='right'caption='[[4gog]], [[Resolution|resolution]] 1.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4gog]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_pneumoniae Klebsiella pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GOG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GOG 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]] 1.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IM2:(5R)-5-[(1S,2R)-1-FORMYL-2-HYDROXYPROPYL]-3-[(2-{[(E)-IMINOMETHYL]AMINO}ETHYL)SULFANYL]-4,5-DIHYDRO-1H-PYRROLE-2-CARBOXYLIC+ACID'>IM2</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=4gog FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gog OCA], [https://pdbe.org/4gog PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gog RCSB], [https://www.ebi.ac.uk/pdbsum/4gog PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gog ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Carbapenem antibiotics have become therapeutics of last resort for the treatment of difficult infections. The emergence of class-A beta-lactamases that have the ability to inactivate carbapenems in the past few years is a disconcerting clinical development in light of the diminished options for treatment of infections. A member of the GES-type beta-lactamase family, GES-1, turns over imipenem poorly, but the GES-5 beta-lactamase is an avid catalyst for turnover of this antibiotic. We report herein high-resolution X-ray structures of the apo GES-5 beta-lactamase and the GES-1 and GES-5 beta-lactamases in complex with imipenem. The latter are the first structures of native class-A carbapenemases with a clinically used carbapenem antibiotic in the active site. The structural information is supplemented by information from molecular dynamics simulations, which collectively for the first time discloses how the second step of catalysis by these enzymes, namely, hydrolytic deacylation of the acyl-enzyme species, takes place effectively in the case of the GES-5 beta-lactamase and significantly less so in GES-1. This information illuminates one evolutionary path that nature has taken in the direction of the inexorable emergence of resistance to carbapenem antibiotics.

Structural basis for progression toward the carbapenemase activity in the GES family of beta-lactamases.,Smith CA, Frase H, Toth M, Kumarasiri M, Wiafe K, Munoz J, Mobashery S, Vakulenko SB J Am Chem Soc. 2012 Dec 5;134(48):19512-5. doi: 10.1021/ja308197j. Epub 2012 Nov , 16. PMID:23148776<ref>PMID:23148776</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4gog" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Klebsiella pneumoniae]]
[[Category: Large Structures]]
[[Category: Munoz J]]
[[Category: Smith CA]]
[[Category: Vakulenko SB]]