6V1M
Structure of NDM-1 bound to QPX7728 at 1.05 A
Summary for 6V1M
| Entry DOI | 10.2210/pdb6v1m/pdb |
| Descriptor | Metallo-beta-lactamase type 2, ZINC ION, (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, ... (4 entities in total) |
| Functional Keywords | carbapenemase, boronate, inhibitor, beta-lactamase, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Klebsiella pneumoniae |
| Total number of polymer chains | 1 |
| Total formula weight | 24972.48 |
| Authors | Pemberton, O.A.,Chen, Y. (deposition date: 2019-11-20, release date: 2020-03-25, Last modification date: 2023-10-11) |
| Primary citation | Hecker, S.J.,Reddy, K.R.,Lomovskaya, O.,Griffith, D.C.,Rubio-Aparicio, D.,Nelson, K.,Tsivkovski, R.,Sun, D.,Sabet, M.,Tarazi, Z.,Parkinson, J.,Totrov, M.,Boyer, S.H.,Glinka, T.W.,Pemberton, O.A.,Chen, Y.,Dudley, M.N. Discovery of Cyclic Boronic Acid QPX7728, an Ultrabroad-Spectrum Inhibitor of Serine and Metallo-beta-lactamases. J.Med.Chem., 63:7491-7507, 2020 Cited by PubMed Abstract: Despite major advances in the β-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 . 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 (). 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 is a promising agent for use in combination with a β-lactam antibiotic for the treatment of a wide range of multidrug resistant Gram-negative bacterial infections, by both intravenous and oral administration. PubMed: 32150407DOI: 10.1021/acs.jmedchem.9b01976 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.05 Å) |
Structure validation
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