5k48
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==VIM-2 Metallo Beta Lactamase in complex with 3-(mercaptomethyl)-[1,1'-biphenyl]-4-carboxylic acid== | ==VIM-2 Metallo Beta Lactamase in complex with 3-(mercaptomethyl)-[1,1'-biphenyl]-4-carboxylic acid== | ||
| - | <StructureSection load='5k48' size='340' side='right' caption='[[5k48]], [[Resolution|resolution]] 1.74Å' scene=''> | + | <StructureSection load='5k48' size='340' side='right'caption='[[5k48]], [[Resolution|resolution]] 1.74Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5k48]] is a 2 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[5k48]] is a 2 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=5K48 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5K48 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=S5Z:4-phenyl-2-(sulfanylmethyl)benzoic+acid'>S5Z</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.744Å</td></tr> |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=S5Z:4-phenyl-2-(sulfanylmethyl)benzoic+acid'>S5Z</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'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5k48 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k48 OCA], [https://pdbe.org/5k48 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5k48 RCSB], [https://www.ebi.ac.uk/pdbsum/5k48 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5k48 ProSAT]</span></td></tr> |
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/Q9K2N0_PSEAI Q9K2N0_PSEAI] | ||
| + | <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. | ||
| + | |||
| + | 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> | ||
| + | |||
| + | 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> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Pseudomonas aeruginosa]] |
| - | [[Category: | + | [[Category: Brem J]] |
| - | [[Category: | + | [[Category: McDonough M]] |
| - | [[Category: | + | [[Category: Schofield C]] |
| - | [[Category: | + | [[Category: Zollman D]] |
| - | + | ||
| - | + | ||
Current revision
VIM-2 Metallo Beta Lactamase in complex with 3-(mercaptomethyl)-[1,1'-biphenyl]-4-carboxylic acid
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