6JKB
Crystal structure of metallo-beta-lactamse, NDM-1, in complex with hydrolyzed ampicillin
Summary for 6JKB
| Entry DOI | 10.2210/pdb6jkb/pdb |
| Descriptor | Metallo-beta-lactamase type 2, ZINC ION, (2R,4S)-2-[(R)-{[(2R)-2-amino-2-phenylacetyl]amino}(carboxy)methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid, ... (4 entities in total) |
| Functional Keywords | hydrolase, antibiotic |
| Biological source | Klebsiella pneumoniae |
| Total number of polymer chains | 2 |
| Total formula weight | 52568.45 |
| Authors | Kamo, T.,Kuroda, K.,Kondo, S.,Hayashi, U.,Fudo, S.,Nukaga, M.,Hoshino, T. (deposition date: 2019-02-28, release date: 2020-03-25, Last modification date: 2023-11-22) |
| Primary citation | Kamo, T.,Kuroda, K.,Kondo, S.,Hayashi, U.,Fudo, S.,Yoneda, T.,Takaya, A.,Nukaga, M.,Hoshino, T. Identification of the Inhibitory Compounds for Metallo-beta-lactamases and Structural Analysis of the Binding Modes. Chem Pharm Bull (Tokyo), 69:1179-1183, 2021 Cited by PubMed Abstract: Metallo-β-lactamases (MBLs) are significant threats to humans because they deteriorate many kinds of β-lactam antibiotics and are key enzymes responsible for multi-drug resistance of bacterial pathogens. As a result of in vitro screening, two compounds were identified as potent inhibitors of two kinds of MBLs: imipenemase (IMP-1) and New Delhi metallo-β-lactamase (NDM-1). The binding structure of one of the identified compounds was clarified by an X-ray crystal analysis in complex with IMP-1, in which two possible binding poses were observed. Molecular dynamics (MD) simulations were performed by building two calculation models from the respective binding poses. The compound was stably bound to the catalytic site during the simulation in one pose. The binding model between NDM-1 and the compound was constructed for MD simulation. Calculation results for NDM-1 were similar to those of IMP-1. The simulation suggested that the binding of the identified inhibitory compound was also durable in the catalytic site of NDM-1. The compound will be a sound basis for the development of the inhibitors for MBLs. PubMed: 34853284DOI: 10.1248/cpb.c21-00611 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.444 Å) |
Structure validation
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