View source for 7ove


==Crystal structure of the VIM-2 acquired metallo-beta-Lactamase in Complex with compound 10 (JMV-7210)==
<StructureSection load='7ove' size='340' side='right'caption='[[7ove]], [[Resolution|resolution]] 1.92&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7ove]] is a 1 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=7OVE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OVE 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]] 1.92&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=UNL:UNKNOWN+LIGAND'>UNL</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=7ove FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ove OCA], [https://pdbe.org/7ove PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ove RCSB], [https://www.ebi.ac.uk/pdbsum/7ove PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ove ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q9K2N0_PSEAI Q9K2N0_PSEAI] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Metallo-beta-lactamases (MBLs) are important contributors of Gram-negative bacteria resistance to beta-lactam antibiotics. MBLs are highly worrying because of their carbapenemase activity, their rapid spread in major human opportunistic pathogens while no clinically useful inhibitor is available yet. In this context, we are exploring the potential of compounds based on the 1,2,4-triazole-3-thione scaffold as an original ligand of the di-zinc active sites of MBLs, and diversely substituted at its positions 4 and 5. Here, we present a new series of compounds substituted at the 4-position by a thioether-containing alkyl chain with a carboxylic and/or an aryl group at its extremity. Several compounds showed broad-spectrum inhibition with Ki values in the muM to sub-muM range against VIM-type enzymes, NDM-1 and IMP-1. The presence of the sulfur and of the aryl group was important for the inhibitory activity and the binding mode of a few compounds in VIM-2 was revealed by X-ray crystallography. Importantly, in vitro antibacterial susceptibility assays showed that several inhibitors were able to potentiate the activity of meropenem on Klebsiella pneumoniae clinical isolates producing VIM-1 or VIM-4, with a potentiation effect of up to 16-fold. Finally, a selected compound was found to only moderately inhibit the di-zinc human glyoxalase II, and several showed no or only moderate toxicity toward several human cells, thus favourably completing a promising behaviour.

1,2,4-Triazole-3-thione compounds with a 4-ethyl alkyl/aryl sulfide substituent are broad-spectrum metallo-beta-lactamase inhibitors with re-sensitization activity.,Legru A, Verdirosa F, Hernandez JF, Tassone G, Sannio F, Benvenuti M, Conde PA, Bossis G, Thomas CA, Crowder MW, Dillenberger M, Becker K, Pozzi C, Mangani S, Docquier JD, Gavara L Eur J Med Chem. 2021 Oct 4;226:113873. doi: 10.1016/j.ejmech.2021.113873. PMID:34626878<ref>PMID:34626878</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7ove" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Pseudomonas aeruginosa]]
[[Category: Benvenuti M]]
[[Category: Docquier JD]]
[[Category: Mangani S]]
[[Category: Marcoccia F]]
[[Category: Pozzi C]]
[[Category: Sannio F]]
[[Category: Tassone G]]
[[Category: Verdirosa F]]