9O2WSummary for 9O2W
| Entry DOI | 10.2210/pdb9o2w/pdb |
| Related | 9D2U 9D54 9D5R 9D8T 9D9N 9DAG 9DB7 |
| Descriptor | Metallo-beta-lactamase type 2, [(7-cyclopropyl-6-fluoro-2-oxo-1,2-dihydroquinolin-4-yl)methyl]phosphonic acid, ZINC ION, ... (4 entities in total) |
| Functional Keywords | inhibitor, beta-lactamase, complex, ndm, hydrolase |
| Biological source | Klebsiella pneumoniae |
| Total number of polymer chains | 2 |
| Total formula weight | 50061.43 |
| Authors | Jacobs, L.M.C.,Chen, Y. (deposition date: 2025-04-04, release date: 2026-03-18, Last modification date: 2026-03-25) |
| Primary citation | Jacobs, L.M.C.,Jaishankar, P.,Zheng, J.,Hantz, E.R.,Lee, I.,Narramneni, K.,Poore, N.,Torres, N.,Jackson, J.K.,Williams, O.,Darch, S.E.,Shaw, L.N.,Chen, Y.,Renslo, A.R. Structure-Based Design of Reversible, Quinoline-2(1 H )‐one Inhibitors of Serine- and Metallo-Carbapenemases. Acs Omega, 11:15316-15327, 2026 Cited by PubMed Abstract: Carbapenems are essential β-lactam antibiotics whose clinical utility is now threatened by emerging carbapenemases, including the Class A serine β-lactamase KPC-2 and the Class B metallo-β-lactamase NDM-1. Here, we describe a comprehensive, structure-based assessment of active-site binding determinants for KPC-2 and NDM-1 in the context of reversible, noncovalent inhibition by a quinoline-2-(1)-one phosphonate scaffold. Systematic substitution of the scaffold core revealed the N1 and C7 positions as most tolerant of diverse substitution, while the less tolerant C3 and C6 positions nevertheless drive affinity and binding mode when modified with a C3-methyl or C6-fluoro substituent, respectively. We also describe biophysical and computational studies aimed at determining the pharmacological significance of the 2:1 ligand binding stoichiometry observed in several NDM-1 complex structures, concluding that only one of these binding events is relevant for potent NDM-1 inhibition. Although the current inhibitors lack significant whole-cell activity, the structural and biochemical findings described provide valuable information for the targeting of evolutionarily and mechanistically diverse carbapenemases. PubMed: 41835567DOI: 10.1021/acsomega.5c12676 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.82 Å) |
Structure validation
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