Catalytic Role of the Metal Ion in the Metallo-beta-lactamase GOB

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2009 Dec 17

PMID 20007696

Citations 18

Authors

Maria-Natalia Lisa

Lars Hemmingsen

Alejandro J Vila

Affiliations

Soon will be listed here.

Abstract

Metallo-beta-lactamases (MbetaLs) stand as one of the main mechanisms of bacterial resistance toward carbapenems. The rational design of an inhibitor for MbetaLs has been limited by an incomplete knowledge of their catalytic mechanism and by the structural diversity of their active sites. Here we show that the MbetaL GOB from Elizabethkingia meningoseptica is active as a monometallic enzyme by using different divalent transition metal ions as surrogates of the native Zn(II) ion. Of the metal derivatives in which Zn(II) is replaced, Co(II) and Cd(II) give rise to the most active enzymes and are shown to occupy the same binding site as the native ion. However, Zn(II) is the only metal ion capable of stabilizing an anionic intermediate that accumulates during nitrocefin hydrolysis, in which the C-N bond has already been cleaved. This finding demonstrates that the catalytic role of the metal ion in GOB is to stabilize the formation of this intermediate prior to nitrogen protonation. This role may be general to all MbetaLs, whereas nucleophile activation by a Zn(II) ion is not a conserved mechanistic feature.

Citing Articles

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