This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
5k48
From Proteopedia
(Difference between revisions)
| (One intermediate revision not shown.) | |||
| Line 1: | Line 1: | ||
==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
| |||||||||||
