4gnu: Difference between revisions
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==Crystal structure of GES-5 carbapenemase== | ==Crystal structure of GES-5 carbapenemase== | ||
<StructureSection load='4gnu' size='340' side='right' caption='[[4gnu]], [[Resolution|resolution]] 1.09Å' scene=''> | <StructureSection load='4gnu' size='340' side='right'caption='[[4gnu]], [[Resolution|resolution]] 1.09Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4gnu]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4gnu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GNU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GNU FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.09Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene></td></tr> | |||
<tr id=' | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4gnu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gnu OCA], [https://pdbe.org/4gnu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gnu RCSB], [https://www.ebi.ac.uk/pdbsum/4gnu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gnu ProSAT]</span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/A0EL75_PSEAI A0EL75_PSEAI] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4gnu" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Beta-lactamase|Beta-lactamase]] | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | |||
[[Category: Pseudomonas aeruginosa]] | [[Category: Pseudomonas aeruginosa]] | ||
[[Category: Smith | [[Category: Smith CA]] | ||
[[Category: Vakulenko | [[Category: Vakulenko SB]] | ||
Latest revision as of 13:02, 30 October 2024
Crystal structure of GES-5 carbapenemaseCrystal structure of GES-5 carbapenemase
Structural highlights
FunctionPublication Abstract from PubMedCarbapenem 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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