3S0Z
Crystal structure of New Delhi Metallo-beta-lactamase (NDM-1)
Summary for 3S0Z
Entry DOI | 10.2210/pdb3s0z/pdb |
Descriptor | Metallo-beta-lactamase, ZINC ION (3 entities in total) |
Functional Keywords | new delhi metallo-beta-lactamase 1, ndm-1, drug resistant, drug discovery, hydrolase |
Biological source | Escherichia coli |
Total number of polymer chains | 2 |
Total formula weight | 47430.77 |
Authors | |
Primary citation | Guo, Y.,Wang, J.,Niu, G.,Shui, W.,Sun, Y.,Zhou, H.,Zhang, Y.,Yang, C.,Lou, Z.,Rao, Z. A structural view of the antibiotic degradation enzyme NDM-1 from a superbug. Protein Cell, 2011 Cited by PubMed Abstract: Gram-negative Enterobacteriaceae with resistance to carbapenem conferred by New Delhi metallo-β-lactamase 1 (NDM-1) are a type of newly discovered antibioticresistant bacteria. The rapid pandemic spread of NDM-1 bacteria worldwide (spreading to India, Pakistan, Europe, America, and Chinese Taiwan) in less than 2 months characterizes these microbes as a potentially major global health problem. The drug resistance of NDM-1 bacteria is largely due to plasmids containing the blaNDM-1 gene shuttling through bacterial populations. The NDM-1 enzyme encoded by the blaNDM-1 gene hydrolyzes β-lactam antibiotics, allowing the bacteria to escape the action of antibiotics. Although the biological functions and structural features of NDM-1 have been proposed according to results from functional and structural investigation of its homologues, the precise molecular characteristics and mechanism of action of NDM-1 have not been clarified. Here, we report the three-dimensional structure of NDM-1 with two catalytic zinc ions in its active site. Biological and mass spectroscopy results revealed that D-captopril can effectively inhibit the enzymatic activity of NDM-1 by binding to its active site with high binding affinity. The unique features concerning the primary sequence and structural conformation of the active site distinguish NDM-1 from other reported metallo-β-lactamases (MBLs) and implicate its role in wide spectrum drug resistance. We also discuss the molecular mechanism of NDM-1 action and its essential role in the pandemic of drug-resistant NDM-1 bacteria. Our results will provide helpful information for future drug discovery targeting drug resistance caused by NDM-1 and related metallo-β-lactamases. PubMed: 21637961DOI: 10.1007/s13238-011-1055-9 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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