4RM5

Structural and mechanistic insights into NDM-1 catalyzed hydrolysis of cephalosporins

Summary for 4RM5

• Entry DOI: 10.2210/pdb4rm5/pdb
• Descriptor: Beta-lactamase NDM-1, ZINC ION (3 entities in total)
• Functional Keywords: hydrolysis of beta-lactam antibiotics, hydrolase
• Biological source: Klebsiella pneumoniae
• Cellular location: Periplasm : C7C422
• Total number of polymer chains: 4
• Total formula weight: 103046.62

Authors

Feng, H.,Ding, J.,Zhu, D.,Liu, X.,Xu, X.,Zhang, Y.,Zang, S.,Wang, D.-C.,Liu, W. (deposition date: 2014-10-19, release date: 2014-11-19, Last modification date: 2023-09-20)

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

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: 25268575
DOI: 10.1021/ja508388e

Experimental method

X-RAY DIFFRACTION (2.1 Å)