8skp: Difference between revisions
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The | ==X-ray structure of the NDM-4 beta-lactamase from Klebsiella pneumonia in complex with 1-hydroxypyridine-2(1H)-thione-6-carboxylic acid== | ||
<StructureSection load='8skp' size='340' side='right'caption='[[8skp]], [[Resolution|resolution]] 1.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8skp]] 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=8SKP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8SKP 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]] 1.3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=WAF:1-hydroxy-6-sulfanylidene-1,6-dihydropyridine-2-carboxylic+acid'>WAF</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=8skp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8skp OCA], [https://pdbe.org/8skp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8skp RCSB], [https://www.ebi.ac.uk/pdbsum/8skp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8skp ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/BLAN1_KLEPN BLAN1_KLEPN] Confers resistance to many beta-lactam antibiotics, including some carbapenems. Does not confer resistance to the polymixin colistin or the fluoroquinolone ciprofloxacin. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The bacterial metallo-beta-lactamases (MBLs) catalyze the inactivation of beta-lactam antibiotics. Identifying novel pharmacophores remains crucial for the clinical development of additional MBL inhibitors. Previously, 1-hydroxypyridine-2(1H)-thione-6-carboxylic acid, hereafter referred to as 1,2-HPT-6-COOH, was reported as a low cytotoxic nanomolar beta-lactamase inhibitor of Verona-integron-encoded metallo-beta-lactamase 2 (VIM-2), capable of rescuing beta-lactam antibiotic activity. In this study, we explore its exact mechanism of inhibition and the extent of its activity through structural characterization of its binding to New Delhi metallo-beta-lactamase 4 (NDM-4) and its inhibitory activity against both NDM-1 and NDM-4. Of all the structure-validated MBL inhibitors available, 1,2-HPT-6-COOH is the first discovered compound capable of forming an octahedral coordination sphere with Zn2 of the binuclear metal center. This unexpected mechanism of action provides important insight for the further optimization of 1,2-HPT-6-COOH and the identification of additional pharmacophores for MBL inhibition. | |||
Characterization of a novel inhibitor for the New Delhi metallo-beta-lactamase-4: implications for drug design and combating bacterial drug resistance.,Thoden JB, Benin BM, Priebe A, Shin WS, Muthyala R, Sham YY, Holden HM J Biol Chem. 2023 Aug 5:105135. doi: 10.1016/j.jbc.2023.105135. PMID:37549809<ref>PMID:37549809</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8skp" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Klebsiella pneumoniae]] | |||
[[Category: Large Structures]] | |||
[[Category: Holden HM]] | |||
[[Category: Thoden JB]] | |||