5LCA
VIM-2 metallo-beta-lactamase in complex with 3-oxo-2-(3-(trifluoromethyl)phenyl)isoindoline-4-carboxylic acid (compound 17)
Summary for 5LCA
| Entry DOI | 10.2210/pdb5lca/pdb |
| Descriptor | Metallo-beta-lactamase VIM-2, ZINC ION, 3-oxidanylidene-2-[3-(trifluoromethyl)phenyl]-1~{H}-isoindole-4-carboxylic acid, ... (5 entities in total) |
| Functional Keywords | metallo-beta-lactamase, inhibitor, complex, antibiotic resistance, hydrolase |
| Biological source | Pseudomonas aeruginosa |
| Total number of polymer chains | 1 |
| Total formula weight | 29265.38 |
| Authors | Li, G.-B.,Brem, J.,McDonough, M.A.,Schofield, C.J. (deposition date: 2016-06-20, release date: 2017-02-15, Last modification date: 2024-01-10) |
| Primary citation | Li, G.B.,Abboud, M.I.,Brem, J.,Someya, H.,Lohans, C.T.,Yang, S.Y.,Spencer, J.,Wareham, D.W.,McDonough, M.A.,Schofield, C.J. NMR-filtered virtual screening leads to non-metal chelating metallo-beta-lactamase inhibitors. Chem Sci, 8:928-937, 2017 Cited by PubMed Abstract: There are no clinically useful inhibitors of metallo-β-lactamases (MBLs), which are a growing problem because they hydrolyse almost all β-lactam antibacterials. Inhibition by most reported MBL inhibitors involves zinc ion chelation. A structure-based virtual screening approach combined with NMR filtering led to the identification of inhibitors of the clinically relevant Verona Integron-encoded MBL (VIM)-2. Crystallographic analyses reveal a new mode of MBL inhibition involving binding adjacent to the active site zinc ions, but which does not involve metal chelation. The results will aid efforts to develop new types of clinically useful inhibitors targeting MBLs/MBL-fold metallo-enzymes involved in antibacterial and anticancer drug resistance. PubMed: 28451231DOI: 10.1039/c6sc04524c PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.93 Å) |
Structure validation
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