5ZGW
Crystal structure of NDM-1 at pH7.5 with 1 molecule per asymmetric unit (crystallized at succinate pH5.5 and soaked at succinate pH7.5)
Summary for 5ZGW
| Entry DOI | 10.2210/pdb5zgw/pdb |
| Related | 5XP6 5ZGI |
| Descriptor | Metallo-beta-lactamase type 2, ZINC ION, HYDROXIDE ION, ... (6 entities in total) |
| Functional Keywords | ndm-1, metallo-beta-lactamase, antibiotic resistent, conformational change, hydrolase |
| Biological source | Klebsiella pneumoniae |
| Total number of polymer chains | 1 |
| Total formula weight | 26244.15 |
| Authors | |
| Primary citation | Zhang, H.,Ma, G.,Zhu, Y.,Zeng, L.,Ahmad, A.,Wang, C.,Pang, B.,Fang, H.,Zhao, L.,Hao, Q. Active-Site Conformational Fluctuations Promote the Enzymatic Activity of NDM-1. Antimicrob. Agents Chemother., 62:-, 2018 Cited by PubMed Abstract: β-Lactam antibiotics are the mainstay for the treatment of bacterial infections. However, elevated resistance to these antibiotics mediated by metallo-β-lactamases (MBLs) has become a global concern. New Delhi metallo-β-lactamase-1 (NDM-1), a newly added member of the MBL family that can hydrolyze almost all β-lactam antibiotics, has rapidly spread all over the world and poses serious clinical threats. Broad-spectrum and mechanism-based inhibitors against all MBLs are highly desired, but the differential mechanisms of MBLs toward different antibiotics pose a great challenge. To facilitate the design of mechanism-based inhibitors, we investigated the active-site conformational changes of NDM-1 through the determination of a series of 15 high-resolution crystal structures in native form and in complex with products and by using biochemical and biophysical studies, site-directed mutagenesis, and molecular dynamics computation. The structural studies reveal the consistency of the active-site conformations in NDM-1/product complexes and the fluctuation in native NDM-1 structures. The enzymatic measurements indicate a correlation between enzymatic activity and the active-site fluctuation, with more fluctuation favoring higher activity. This correlation is further validated by structural and enzymatic studies of the Q123G mutant. Our combinational studies suggest that active-site conformational fluctuation promotes the enzymatic activity of NDM-1, which may guide further mechanism studies and inhibitor design. PubMed: 30150473DOI: 10.1128/AAC.01579-18 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (0.95 Å) |
Structure validation
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