Catalysis of transthiolacylation in the active centers of dihydrolipoamide acyltransacetylase components of 2-oxo acid dehydrogenase complexes.

ABSTRACT: The Escherichia coli 2-oxoglutarate dehydrogenase complex (OGDHc) comprises multiple copies of three enzymes-E1o, E2o, and E3-and transthioesterification takes place within the catalytic domain of E2o. The succinyl group from the thiol ester of S8-succinyldihydrolipoyl-E2o is transferred to the thiol group of coenzyme A (CoA), forming the all-important succinyl-CoA. Here, we report mechanistic studies of enzymatic transthioesterification on OGDHc. Evidence is provided for the importance of His375 and Asp374 in E2o for the succinyl transfer reaction. The magnitude of the rate acceleration provided by these residues (54-fold from each with alanine substitution) suggests a role in stabilization of the symmetrical tetrahedral oxyanionic intermediate by formation of two hydrogen bonds, r

SUBMITTER: Chakraborty J 

PROVIDER: S-EPMC5986005 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature