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5lsc
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=5lsc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lsc OCA], [http://pdbe.org/5lsc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lsc RCSB], [http://www.ebi.ac.uk/pdbsum/5lsc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lsc 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=5lsc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lsc OCA], [http://pdbe.org/5lsc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lsc RCSB], [http://www.ebi.ac.uk/pdbsum/5lsc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lsc ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The increasing number of pathogens expressing metallo-beta-lactamases (MBLs), and in this way achieving resistance to beta-lactam antibiotics, is a significant threat to global public health. A promising strategy to treat such resistant pathogens is the co-administration of MBL inhibitors together with beta-lactam antibiotics. However, an MBL inhibitor suitable for clinical use has not yet been identified. Verona integron-encoded metallo-beta-lactamase 2 (VIM-2) is a widespread MBL with a broad substrate spectrum and hence is an interesting drug target for the treatment of beta-lactam-resistant infections. In this study, three triazolylthioacetamides were tested as inhibitors of VIM-2. One of the tested compounds showed clear inhibition of VIM-2, with an IC50 of 20 microM. The crystal structure of the inhibitor in complex with VIM-2 was obtained by DMSO-free co-crystallization and was solved at a resolution of 1.50 A. To our knowledge, this is the first structure of a triazolylthioacetamide inhibitor in complex with an MBL. Analysis of the structure shows that the inhibitor binds to the two zinc ions in the active site of VIM-2 and revealed detailed information on the interactions involved. Furthermore, the crystal structure showed that binding of the inhibitor induced a conformational change of the conserved residue Trp87. | ||
| + | |||
| + | The structure of the metallo-beta-lactamase VIM-2 in complex with a triazolylthioacetamide inhibitor.,Christopeit T, Yang KW, Yang SK, Leiros HK Acta Crystallogr F Struct Biol Commun. 2016 Nov 1;72(Pt 11):813-819. Epub 2016, Oct 24. PMID:27834790<ref>PMID:27834790</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5lsc" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 03:59, 30 August 2017
The structure of the metallo-beta-lactamase VIM-2 in complex with a triazolylthioacetamide inhibitor
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