Modulation of succinyl-CoA:3-ketoacid CoA transferase activity by a single amino acid residue in acetate:succinate CoA transferase from Trypanosoma brucei, the causative agent of African sleeping sickness.

ABSTRACT: Trypanosomatids are protozoan parasites that remain a global health challenge due to the limited efficacy, safety, and durability of current treatments. Acetate: succinate CoA transferase (ASCT), together with succinyl-CoA synthase (SCS), forms the ASCT/SCS cycle that fuels ATP production and generates acetate, a central metabolic intermediate essential for mitochondrial pathways in these parasites. Although Trypanosoma brucei ASCT (TbASCT) shares 52% amino acid identity with mammalian succinyl-CoA:3-ketoacid CoA transferase (mSCOT), the latter catalyzes a rate-limiting step of ketone body catabolism. Because ASCT and SCOT perform distinct reactions, understanding their mechanistic divergence is crucial for identifying parasite-specific vulnerabilities and advancing selective drug discover

SUBMITTER: Mochizuki K 

PROVIDER: S-EPMC12817287 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature