5k48
From Proteopedia
(Difference between revisions)
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5k48 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k48 OCA], [http://pdbe.org/5k48 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5k48 RCSB], [http://www.ebi.ac.uk/pdbsum/5k48 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5k48 ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5k48 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k48 OCA], [http://pdbe.org/5k48 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5k48 RCSB], [http://www.ebi.ac.uk/pdbsum/5k48 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5k48 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Zinc ion-dependent beta-lactamases (MBLs) catalyze the hydrolysis of almost all beta-lactam antibiotics and resist the action of clinically available beta-lactamase inhibitors. We report how application of in silico fragment-based molecular design employing thiol-mediated metal anchorage leads to potent MBL inhibitors. The new inhibitors manifest potent inhibition of clinically important B1 subfamily MBLs, including the widespread NDM-1, IMP-1, and VIM-2 enzymes; with lower potency, some of them also inhibit clinically relevant Class A and D serine-beta-lactamases. The inhibitors show selectivity for bacterial MBL enzymes compared to that for human MBL fold nucleases. Cocrystallization of one inhibitor, which shows potentiation of Meropenem activity against MBL-expressing Enterobacteriaceae, with VIM-2 reveals an unexpected binding mode, involving interactions with residues from conserved active site bordering loops. | ||
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| + | In Silico Fragment-Based Design Identifies Subfamily B1 Metallo-beta-lactamase Inhibitors.,Cain R, Brem J, Zollman D, McDonough MA, Johnson RM, Spencer J, Makena A, Abboud MI, Cahill S, Lee SY, McHugh PJ, Schofield CJ, Fishwick CWG J Med Chem. 2018 Jan 10. doi: 10.1021/acs.jmedchem.7b01728. PMID:29271657<ref>PMID:29271657</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5k48" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 08:07, 17 January 2018
VIM-2 Metallo Beta Lactamase in complex with 3-(mercaptomethyl)-[1,1'-biphenyl]-4-carboxylic acid
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