4zam: Difference between revisions
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<StructureSection load='4zam' size='340' side='right'caption='[[4zam]], [[Resolution|resolution]] 1.42Å' scene=''> | <StructureSection load='4zam' size='340' side='right'caption='[[4zam]], [[Resolution|resolution]] 1.42Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4zam]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4zam]] is a 1 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=4ZAM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZAM FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MA4:CYCLOHEXYL-HEXYL-BETA-D-MALTOSIDE'>MA4</scene>, <scene name='pdbligand=NXL:(2S,5R)-1-FORMYL-5-[(SULFOOXY)AMINO]PIPERIDINE-2-CARBOXAMIDE'>NXL</scene | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MA4:CYCLOHEXYL-HEXYL-BETA-D-MALTOSIDE'>MA4</scene>, <scene name='pdbligand=NXL:(2S,5R)-1-FORMYL-5-[(SULFOOXY)AMINO]PIPERIDINE-2-CARBOXAMIDE'>NXL</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=4zam FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zam OCA], [https://pdbe.org/4zam PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zam RCSB], [https://www.ebi.ac.uk/pdbsum/4zam PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zam 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/BLA1_KLEPN BLA1_KLEPN] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Klebsiella pneumoniae]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Krishnan N]] | |||
[[Category: Krishnan | [[Category: Van den Akker F]] | ||
[[Category: | |||
Revision as of 10:46, 10 May 2023
Crystal structure of SHV-1 beta-lactamase bound to avibactamCrystal structure of SHV-1 beta-lactamase bound to avibactam
Structural highlights
FunctionPublication Abstract from PubMedbeta-Lactamase inhibition is an important clinical strategy in overcoming beta-lactamase-mediated resistance to beta-lactam antibiotics in Gram negative bacteria. A new beta-lactamase inhibitor, avibactam, is entering the clinical arena and promising to be a major step forward in our antibiotic armamentarium. Avibactam has remarkable broad-spectrum activity in being able to inhibit classes A, C, and some class D beta-lactamases. We present here structural investigations into class A beta-lactamase inhibition by avibactam as we report the crystal structures of SHV-1, the chromosomal penicillinase of Klebsiella pneumoniae, and KPC-2, an acquired carbapenemase found in the same pathogen, complexed with avibactam. The 1.80 A KPC-2 and 1.42 A resolution SHV-1 beta-lactamase avibactam complex structures reveal avibactam covalently bonded to the catalytic S70 residue. Analysis of the interactions and chair-shaped conformation of avibactam bound to the active sites of KPC-2 and SHV-1 provides structural insights into recently laboratory-generated amino acid substitutions that result in resistance to avibactam in KPC-2 and SHV-1. Furthermore, we observed several important differences in the interactions with amino acid residues, in particular that avibactam forms hydrogen bonds to S130 in KPC-2 but not in SHV-1, that can possibly explain some of the different kinetic constants of inhibition. Our observations provide a possible reason for the ability of KPC-2 beta-lactamase to slowly desulfate avibactam with a potential role for the stereochemistry around the N1 atom of avibactam and/or the presence of an active site water molecule that could aid in avibactam desulfation, an unexpected consequence of novel inhibition chemistry. Inhibition of Klebsiella beta-Lactamases (SHV-1 and KPC-2) by Avibactam: A Structural Study.,Krishnan NP, Nguyen NQ, Papp-Wallace KM, Bonomo RA, van den Akker F PLoS One. 2015 Sep 4;10(9):e0136813. doi: 10.1371/journal.pone.0136813., eCollection 2015. PMID:26340563[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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