The mechanism of NDM-1-catalyzed carbapenem hydrolysis is distinct from that of penicillin or cephalosporin hydrolysis.

ABSTRACT: New Delhi metallo-β-lactamases (NDMs), the recent additions to metallo-β-lactamases (MBLs), pose a serious public health threat due to its highly efficient hydrolysis of β-lactam antibiotics and rapid worldwide dissemination. The MBL-hydrolyzing mechanism for carbapenems is less studied than that of penicillins and cephalosporins. Here, we report crystal structures of NDM-1 in complex with hydrolyzed imipenem and meropenem, at resolutions of 1.80-2.32 Å, together with NMR spectra monitoring meropenem hydrolysis. Three enzyme-intermediate/product derivatives, EI₁, EI₂, and EP, are trapped in these crystals. Our structural data reveal double-bond tautomerization from Δ² to Δ¹, absence of a bridging water molecule and an exclusive β-diastereomeric p

SUBMITTER: Feng H 

PROVIDER: S-EPMC5740130 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature