9MB4
Metal Beta Lactamase NDM-1 in Complex with Dual MBL/SBL Inhibitor 14
This is a non-PDB format compatible entry.
Summary for 9MB4
| Entry DOI | 10.2210/pdb9mb4/pdb |
| Descriptor | Metallo-beta-lactamase type 2, ZINC ION, 3,3-bis(oxidanyl)-9-[(4-thiophen-2-yl-1,2,3-triazol-1-yl)methyl]-2,5-dioxa-3-boranuidabicyclo[4.4.0]deca-1(6),7,9-triene-10-carboxylic acid, ... (4 entities in total) |
| Functional Keywords | beta lactamase, metallo beta lactamase ndm-1, carbapenemase, hydrolase |
| Biological source | Klebsiella pneumoniae |
| Total number of polymer chains | 4 |
| Total formula weight | 104318.97 |
| Authors | |
| Primary citation | Yang, Z.B.,Wei, S.Q.,Wang, Y.G.,Dong, X.M.,Xu, H.X.,Li, X.L.,Peng, J.,Yin, R.C.,Li, G.B. Structural Optimization of Bicyclic Oxo-Boronates as Dual Metallo- and Serine-beta-Lactamase Inhibitors. J.Med.Chem., 68:21807-21828, 2025 Cited by PubMed Abstract: Gram-negative bacterial resistance to β-lactam antibiotics is a growing clinical problem, largely driven by the production of metallo-β-lactamases (MBLs) and serine-β-lactamases (SBLs). Developing dual inhibitors targeting both MBLs and SBLs has emerged as a focus in the fight against β-lactam resistance. We previously identified the bicyclic oxo-boronate as a dual MBL/SBL inhibitor through molecular generation based on the binding mode of carbapenem tetrahedral intermediates. Herein, we report the structural optimization of , yielding new bicyclic oxo-boronates with potent dual MBL/SBL inhibition, some of which could potentiate Meropenem efficacy against carbapenem-resistant Gram-negative superbugs. X-ray crystallography revealed a common binding mode of bicyclic oxo-boronates with VIM-2/NDM-1 MBL and OXA-48 SBL, mimicking the binding of carbapenem intermediates. exhibited pharmacokinetic characteristics similar to Meropenem and manifested efficacy when combined with Meropenem in a murine sepsis model. This work provides the basis for developing oxo-boronate-based inhibitors targeting MBLs/SBLs and other relevant targets. PubMed: 41082617DOI: 10.1021/acs.jmedchem.5c02230 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.441 Å) |
Structure validation
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