The Roles of Coenzyme A Binding Pocket Residues in Short and Medium Chain Acyl-CoA Synthetases.

ABSTRACT: Short- and medium-chain acyl-CoA synthetases catalyze similar two-step reactions in which acyl substrate and ATP bind to form an enzyme-bound acyl-adenylate, then CoA binds for formation of the acyl-CoA product. We investigated the roles of active site residues in CoA binding in acetyl-CoA synthetase (Acs) and a medium-chain acyl-CoA synthetase (Macs) that uses 2-methylbutyryl-CoA. Three highly conserved residues, Arg¹⁹³, Arg⁵²⁸, and Arg⁵⁸⁶ of Methanothermobacter thermautotrophicus Acs (Acs_Mt), are predicted to form important interactions with the 5'- and 3'-phosphate groups of CoA. Kinetic characterization of Acs_Mt variants altered at each of these positions indicates these Arg residues play a critical role in CoA binding and c

SUBMITTER: Meng Y 

PROVIDER: S-EPMC10455477 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature