9ZOWSummary for 9ZOW
| Entry DOI | 10.2210/pdb9zow/pdb |
| Descriptor | Beta-lactamase OXA-23, CARBON DIOXIDE, (2S)-2-[(1S,2R)-1-carboxy-2-hydroxypropyl]-4-{[(3S)-2,3-dihydroazet-3-yl]sulfanyl}-2-methyl-2H-pyrrole-5-carboxylic acid, ... (5 entities in total) |
| Functional Keywords | antibiotic resistance, beta-lactamase, inhibitor, hydrolase-inhibitor complex, hydrolase/inhibitor |
| Biological source | Acinetobacter baumannii |
| Total number of polymer chains | 1 |
| Total formula weight | 31604.50 |
| Authors | Smith, C.A.,Maggiolo, A.O.,Vakulenko, S.B.,Toth, M. (deposition date: 2025-12-16, release date: 2026-01-14, Last modification date: 2026-08-05) |
| Primary citation | Toth, M.,Stewart, N.K.,Maggiolo, A.O.,Quan, P.,Khan, M.M.K.,Cox, J.,Castro Cabello, M.,Buynak, J.D.,Smith, C.A.,Vakulenko, S.B. The Novel Carbapenem, JDB/PQ-1-219, Has Potent Broad Spectrum Activity against Multi-Drug Resistant Acinetobacter baumannii. Acs Infect Dis., 12:2396-2406, 2026 Cited by PubMed Abstract: Carbapenem resistance in , driven largely by class D, along with class A and class B β-lactamases, has severely compromised the utility of these last resort antibiotics. As a result, infections caused by such pathogens are characterized by extremely high mortality rates. Here we describe the antimicrobial activity of the novel C5 methyl-substituted carbapenem JDB/PQ-1-219 against multidrug resistant and the mechanism of its interaction with its major carbapenemase, OXA-23. JDB/PQ-1-219 exhibits potent antimicrobial activity against producing various carbapenemases, with MICs that are all in the clinically susceptible range. The compound has unrestricted ingress through porins and avoids egress by efflux pumps, a unique property when compared to all commercial carbapenems. Kinetic experiments demonstrated that unlike for other carbapenems, acylation of OXA-23 by JDB/PQ-1-219 is monophasic, and mass spectrometry studies showed that this results from the conversion of all enzyme into a reversible tetrahedral intermediate which gradually transitions into the stable acyl-enzyme complex. No deacylation of this complex is observed over a physiologically relevant time period, making JDB/PQ-1-219 an extremely potent inhibitor of OXA-23. Time-resolved crystallography revealed fine details of active site dynamics, leading to complete inhibition of the enzyme. Together, these studies identify JDB/PQ-1-219 as a uniquely effective novel carbapenem with clinically significant levels of activity against multidrug resistant . PubMed: 42311063DOI: 10.1021/acsinfecdis.6c00415 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.7 Å) |
Structure validation
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