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| | <StructureSection load='6v1j' size='340' side='right'caption='[[6v1j]], [[Resolution|resolution]] 1.30Å' scene=''> | | <StructureSection load='6v1j' size='340' side='right'caption='[[6v1j]], [[Resolution|resolution]] 1.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6v1j]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_pneumoniae"_(schroeter_1886)_flugge_1886 "bacillus pneumoniae" (schroeter 1886) flugge 1886]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V1J OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6V1J FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6v1j]] is a 1 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=6V1J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6V1J FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=RM9:(1aR,7bS)-5-fluoro-2-hydroxy-1,1a,2,7b-tetrahydrocyclopropa[c][1,2]benzoxaborinine-4-carboxylic+acid'>RM9</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.3Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">bla, kpc, kpc1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=573 "Bacillus pneumoniae" (Schroeter 1886) Flugge 1886])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=QNA:(2~{S},4~{R})-9-fluoranyl-5,5-bis(oxidanyl)-6-oxa-5-boranuidatricyclo[5.4.0.0^{2,4}]undeca-1(11),7,9-triene-8-carboxylic+acid'>QNA</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>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] </span></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=6v1j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v1j OCA], [https://pdbe.org/6v1j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6v1j RCSB], [https://www.ebi.ac.uk/pdbsum/6v1j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6v1j ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6v1j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v1j OCA], [http://pdbe.org/6v1j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6v1j RCSB], [http://www.ebi.ac.uk/pdbsum/6v1j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6v1j ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BLKPC_KLEPN BLKPC_KLEPN]] Hydrolyzes carbapenems, penicillins, cephalosporins and monobactams with varying efficiency. | + | [https://www.uniprot.org/uniprot/BLKPC_KLEPN BLKPC_KLEPN] Hydrolyzes carbapenems, penicillins, cephalosporins and monobactams with varying efficiency. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Beta-lactamase]] | + | [[Category: Klebsiella pneumoniae]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Chen, Y]] | + | [[Category: Chen Y]] |
| - | [[Category: Pemberton, O A]] | + | [[Category: Pemberton OA]] |
| - | [[Category: Boronate]]
| + | |
| - | [[Category: Carbapenemase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| - | [[Category: Inhibitor]]
| + | |
| Structural highlights
Function
BLKPC_KLEPN Hydrolyzes carbapenems, penicillins, cephalosporins and monobactams with varying efficiency.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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. Discovery of Cyclic Boronic Acid QPX7728, an Ultra-broad-spectrum Inhibitor of Serine and Metallo Beta-lactamases. J Med Chem. 2020 Mar 9. doi: 10.1021/acs.jmedchem.9b01976. PMID:32150407 doi:http://dx.doi.org/10.1021/acs.jmedchem.9b01976
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