Structural basis for inhibition of Mycobacterium tuberculosis α-methylacyl-CoA racemase by 2-arylthiopropanoyl-CoA inhibitor analogs.

ABSTRACT: α-Methylacyl-CoA racemase (AMACR; P504S) is a pivotal enzyme involved in the β-oxidation of branched-chain fatty acids and bile acid intermediates, catalyzing the conversion between (2R)- and (2S)-2-methylacyl-CoA thioester epimers. The AMACR reaction enables downstream catabolism of these thioesters via stereospecific enzymes within the β-oxidation pathway. The AMACR homolog in Mycobacterium tuberculosis (MCR) has emerged as a tractable model for dissecting the mechanistic underpinnings of the racemization reaction and presents a promising therapeutic target given the pathogen's dependence on lipid metabolism for persistence and virulence. Previously, we reported the detailed molecular structure of wild-type MCR and in complex with a diverse set of acyl-CoA substrates. They revealed conse

SUBMITTER: Mojanaga OO 

PROVIDER: S-EPMC12682127 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature