6v1o: Difference between revisions
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==Structure of OXA-48 bound to QPX7728 at 1.80 A== | |||
<StructureSection load='6v1o' size='340' side='right'caption='[[6v1o]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6v1o]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_pneumoniae Klebsiella pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V1O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6V1O 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]] 1.8Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=RM9:(1aR,7bS)-5-fluoro-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic+acid'>RM9</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=6v1o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v1o OCA], [https://pdbe.org/6v1o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6v1o RCSB], [https://www.ebi.ac.uk/pdbsum/6v1o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6v1o ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q6XEC0_KLEPN Q6XEC0_KLEPN] | |||
<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 6v1o" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Klebsiella pneumoniae]] | |||
[[Category: Large Structures]] | |||
[[Category: Chen Y]] | |||
[[Category: Pemberton OA]] | |||
Latest revision as of 11:02, 11 October 2023
Structure of OXA-48 bound to QPX7728 at 1.80 AStructure of OXA-48 bound to QPX7728 at 1.80 A
Structural highlights
FunctionPublication Abstract from PubMedDespite 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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