9mas | pdb_00009mas

Metal Beta Lactamase VIM-2 in Complex with Dual MBL/SBL Inhibitor 3

spinqualitylabelsall models 9mas, resolution 1.76Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9mas is a 2 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.757Å Ligands: A1ENM, FMT, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BLBV2_ECOLX Class B beta-lactamase which confers resistance to the beta-lactam antibiotics, including penicillins, cephalosporins and carbapenems (PubMed:20498317, PubMed:31744917). Acts via hydrolysis of the beta-lactam ring (PubMed:20498317, PubMed:24965651). Has penicillin-, cephalosporin- and carbapenem-hydrolyzing activities (PubMed:20498317, PubMed:24965651). Publication Abstract from PubMed Gram-negative bacterial resistance to beta-lactam antibiotics is a growing clinical problem, largely driven by the production of metallo-beta-lactamases (MBLs) and serine-beta-lactamases (SBLs). Developing dual inhibitors targeting both MBLs and SBLs has emerged as a focus in the fight against beta-lactam resistance. We previously identified the bicyclic oxo-boronate CB1 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 CB1, 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. YL6113 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. Structural Optimization of Bicyclic Oxo-Boronates as Dual Metallo- and Serine-beta-Lactamase Inhibitors.,Yang ZB, Wei SQ, Wang YG, Dong XM, Xu HX, Li XL, Peng J, Yin RC, Li GB J Med Chem. 2025 Oct 23;68(20):21807-21828. doi: 10.1021/acs.jmedchem.5c02230. , Epub 2025 Oct 13. PMID:41082617 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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