5lm6: Difference between revisions
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==VIM-2 metallo-beta-lactamase in complex with 2-(3-fluoro-4-hydroxyphenyl)-3-oxoisoindoline-4-carboxylic acid (compound 35)== | |||
<StructureSection load='5lm6' size='340' side='right'caption='[[5lm6]], [[Resolution|resolution]] 1.17Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5lm6]] 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=5LM6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LM6 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]] 1.17Å</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=H32:2-(3-FLUORANYL-4-OXIDANYL-PHENYL)-3-OXIDANYLIDENE-1~{H}-ISOINDOLE-4-CARBOXYLIC+ACID'>H32</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=5lm6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lm6 OCA], [https://pdbe.org/5lm6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lm6 RCSB], [https://www.ebi.ac.uk/pdbsum/5lm6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lm6 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q9K2N0_PSEAI Q9K2N0_PSEAI] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
There are no clinically useful inhibitors of metallo-beta-lactamases (MBLs), which are a growing problem because they hydrolyse almost all beta-lactam antibacterials. Inhibition by most reported MBL inhibitors involves zinc ion chelation. A structure-based virtual screening approach combined with NMR filtering led to the identification of inhibitors of the clinically relevant Verona Integron-encoded MBL (VIM)-2. Crystallographic analyses reveal a new mode of MBL inhibition involving binding adjacent to the active site zinc ions, but which does not involve metal chelation. The results will aid efforts to develop new types of clinically useful inhibitors targeting MBLs/MBL-fold metallo-enzymes involved in antibacterial and anticancer drug resistance. | |||
NMR-filtered virtual screening leads to non-metal chelating metallo-beta-lactamase inhibitors.,Li GB, Abboud MI, Brem J, Someya H, Lohans CT, Yang SY, Spencer J, Wareham DW, McDonough MA, Schofield CJ Chem Sci. 2017 Feb 1;8(2):928-937. doi: 10.1039/c6sc04524c. Epub 2016 Dec 14. PMID:28451231<ref>PMID:28451231</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5lm6" style="background-color:#fffaf0;"></div> | ||
[[Category: Li | |||
[[Category: | ==See Also== | ||
[[Category: | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | ||
[[Category: Someya | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Pseudomonas aeruginosa]] | |||
[[Category: Brem J]] | |||
[[Category: Li G-B]] | |||
[[Category: McDonough MA]] | |||
[[Category: Schofield CJ]] | |||
[[Category: Someya H]] | |||
Latest revision as of 21:34, 18 October 2023
VIM-2 metallo-beta-lactamase in complex with 2-(3-fluoro-4-hydroxyphenyl)-3-oxoisoindoline-4-carboxylic acid (compound 35)VIM-2 metallo-beta-lactamase in complex with 2-(3-fluoro-4-hydroxyphenyl)-3-oxoisoindoline-4-carboxylic acid (compound 35)
Structural highlights
FunctionPublication Abstract from PubMedThere are no clinically useful inhibitors of metallo-beta-lactamases (MBLs), which are a growing problem because they hydrolyse almost all beta-lactam antibacterials. Inhibition by most reported MBL inhibitors involves zinc ion chelation. A structure-based virtual screening approach combined with NMR filtering led to the identification of inhibitors of the clinically relevant Verona Integron-encoded MBL (VIM)-2. Crystallographic analyses reveal a new mode of MBL inhibition involving binding adjacent to the active site zinc ions, but which does not involve metal chelation. The results will aid efforts to develop new types of clinically useful inhibitors targeting MBLs/MBL-fold metallo-enzymes involved in antibacterial and anticancer drug resistance. NMR-filtered virtual screening leads to non-metal chelating metallo-beta-lactamase inhibitors.,Li GB, Abboud MI, Brem J, Someya H, Lohans CT, Yang SY, Spencer J, Wareham DW, McDonough MA, Schofield CJ Chem Sci. 2017 Feb 1;8(2):928-937. doi: 10.1039/c6sc04524c. Epub 2016 Dec 14. PMID:28451231[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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