6v1p: Difference between revisions
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==Structure of VIM-2 bound to QPX7728 at 1.20 A== | |||
<StructureSection load='6v1p' size='340' side='right'caption='[[6v1p]], [[Resolution|resolution]] 1.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6v1p]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V1P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6V1P FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=QNA:(1~{a}~{R},7~{b}~{S})-5-fluoranyl-2,2-bis(oxidanyl)-1~{a},7~{b}-dihydro-1~{H}-cyclopropa[c][1,2]benzoxaborinine-4-carboxylic+acid'>QNA</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6v1p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v1p OCA], [http://pdbe.org/6v1p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6v1p RCSB], [http://www.ebi.ac.uk/pdbsum/6v1p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6v1p ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Despite major advances in the beta-lactamase inhibitor field, certain enzymes remain refractory to inhibition by agents recently introduced. Most important among these are the Class B (metallo) enzyme NDM-1 of Enterobacteriaceae and the Class D (OXA) enzymes of Acinetobacter baumannii. Continuing the boronic acid program that led to vaborbactam, efforts were directed toward expanding the spectrum to allow treatment of a wider range of organisms. Through key structural modifications of a bicyclic lead, stepwise gains in spectrum of inhibition were achieved, ultimately resulting in QPX7728 (35). This compound displays a remarkably broad spectrum of inhibition, including Class B and Class D enzymes, and is little affected by porin modifications and efflux. Compound 35 is a promising agent for use in combination with a beta-lactam antibiotic for the treatment of a wide range of multidrug resistant gram-negative bacterial infections, by both intravenous and oral administration. | |||
Discovery of Cyclic Boronic Acid QPX7728, an Ultra-broad-spectrum Inhibitor of Serine and Metallo Beta-lactamases.,Hecker SJ, Reddy KR, Lomovskaya O, Griffith DC, Rubio-Aparicio D, Nelson K, Tsivkovski R, Sun D, Sabet M, Tarazi Z, Parkinson J, Totrov M, Boyer SH, Glinka TW, Pemberton OA, Chen Y, Dudley MN J Med Chem. 2020 Mar 9. doi: 10.1021/acs.jmedchem.9b01976. PMID:32150407<ref>PMID:32150407</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6v1p" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Chen, Y]] | |||
[[Category: Pemberton, O A]] | |||
[[Category: Beta-lactamase]] | |||
[[Category: Boronate]] | |||
[[Category: Carbapenemase]] | |||
[[Category: Hydrolase]] | |||
[[Category: Hydrolase-hydrolase inhibitor complex]] | |||
[[Category: Inhibitor]] | |||
Revision as of 10:23, 27 March 2020
Structure of VIM-2 bound to QPX7728 at 1.20 A
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