Structure and reactivity of Bacillus subtilis MenD catalyzing the first committed step in menaquinone biosynthesis.

ABSTRACT: The first committed step in the classical biosynthetic route to menaquinone (vitamin K(2)) is a Stetter-like conjugate addition of alpha-ketoglutarate with isochorismate. This reaction is catalyzed by the thiamine diphosphate and metal-ion-dependent 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexadiene-1-carboxylate synthase (MenD). The medium-resolution (2.35 A) crystal structure of Bacillus subtilis MenD with cofactor and Mn(2+) has been determined. Based on structure-sequence comparisons and modeling, a two-stage mechanism that is primarily driven by the chemical properties of the cofactor is proposed. Hypotheses for the molecular determinants of substrate recognition were formulated. Five basic residues (Arg32, Arg106, Arg409, Arg428, and Lys299) are postulated to interact with carboxyla

SUBMITTER: Dawson A 

PROVIDER: S-EPMC2914249 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature