Catalytic role of the metal ion in the metallo-beta-lactamase GOB.

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 t

SUBMITTER: Lisa MN 

PROVIDER: S-EPMC2836117 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature