4RL0
Structural and mechanistic insights into NDM-1 catalyzed hydrolysis of cephalosporins
Summary for 4RL0
| Entry DOI | 10.2210/pdb4rl0/pdb |
| Descriptor | Beta-lactamase NDM-1, ZINC ION, (2R,5S)-5-[(carbamoyloxy)methyl]-2-[(R)-carboxy{[(2Z)-2-(furan-2-yl)-2-(methoxyimino)acetyl]amino}methyl]-5,6-dihydro-2H-1,3-thiazine-4-carboxylic acid, ... (4 entities in total) |
| Functional Keywords | ndm-1 antibiotic hydrolysis, hydrolase |
| Biological source | Klebsiella pneumoniae |
| Cellular location | Periplasm : C7C422 |
| Total number of polymer chains | 2 |
| Total formula weight | 52410.08 |
| Authors | |
| Primary citation | Feng, H.,Ding, J.,Zhu, D.,Liu, X.,Xu, X.,Zhang, Y.,Zang, S.,Wang, D.C.,Liu, W. Structural and Mechanistic Insights into NDM-1 Catalyzed Hydrolysis of Cephalosporins. J.Am.Chem.Soc., 136:14694-14697, 2014 Cited by PubMed Abstract: Cephalosporins constitute a large class of β-lactam antibiotics clinically used as antimicrobial drugs. New Dehli metallo-β-lactamase (NDM-1) poses a global threat to human health as it confers on bacterial pathogen resistance to almost all β-lactams, including penicillins, cephalosporins, and carbapenems. Here we report the first crystal structures of NDM-1 in complex with cefuroxime and cephalexin, as well as NMR spectra monitoring cefuroxime and cefixime hydrolysis catalyzed by NDM-1. Surprisingly, cephalosporoate intermediates were captured in both crystal structures determined at 1.3 and 2.0 Å. These results provide detailed information concerning the mechanism and pathways of cephalosporin hydrolysis. We also present the crystal structure and enzyme assays of a D124N mutant, which reveals that D124 most likely plays a more structural than catalytic role. PubMed: 25268575DOI: 10.1021/ja508388e PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.3 Å) |
Structure validation
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