3WXC
Crystal Structure of IMP-1 metallo-beta-lactamase complexed with a 3-aminophtalic acid inhibitor
Summary for 3WXC
| Entry DOI | 10.2210/pdb3wxc/pdb |
| Descriptor | Beta-lactamase, ZINC ION, 3-(4-hydroxypiperidin-1-yl)benzene-1,2-dicarboxylic acid, ... (4 entities in total) |
| Functional Keywords | lactamase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Pseudomonas aeruginosa |
| Total number of polymer chains | 2 |
| Total formula weight | 49862.17 |
| Authors | Saito, J.,Watanabe, T.,Yamada, M. (deposition date: 2014-07-29, release date: 2014-10-15, Last modification date: 2024-04-03) |
| Primary citation | Hiraiwa, Y.,Saito, J.,Watanabe, T.,Yamada, M.,Morinaka, A.,Fukushima, T.,Kudo, T. X-ray crystallographic analysis of IMP-1 metallo-beta-lactamase complexed with a 3-aminophthalic acid derivative, structure-based drug design, and synthesis of 3,6-disubstituted phthalic acid derivative inhibitors Bioorg.Med.Chem.Lett., 24:4891-4894, 2014 Cited by PubMed Abstract: 3-(4-Hydroxypiperidine-1-yl) phthalic acid 1 shows potent inhibitory activity against metallo-β-lactamase, which is known to inactivate β-lactam antibiotics such as carbapenems. Here, the structure of co-crystals of the metallo-β-lactamase IMP-1 and 1 was first analyzed by X-ray crystallography, and then used for structure-based drug design. Four novel compounds bearing substituents at the 6-position were synthesized to produce 3,6-disubstituted phthalic acid derivatives, and their IMP-1 inhibitory activity and synergistic effect with the carbapenem biapenem (BIPM) were evaluated. 3,6-Disubstituted phthalic acid derivatives showed potent IMP-1 inhibitory activity. In particular, compound 13 showed 10-fold higher IMP-1 inhibitory activity as compared with the parent derivative 1. PubMed: 25246278DOI: 10.1016/j.bmcl.2014.08.039 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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