A Catalytic Trisulfide in Human Sulfide Quinone Oxidoreductase Catalyzes Coenzyme A Persulfide Synthesis and Inhibits Butyrate Oxidation.

ABSTRACT: Mitochondrial sulfide quinone oxidoreductase (SQR) catalyzes the oxidation of H₂S to glutathione persulfide with concomitant reduction of CoQ₁₀. We report herein that the promiscuous activity of human SQR supported the conversion of CoA to CoA-SSH (CoA-persulfide), a potent inhibitor of butyryl-CoA dehydrogenase, and revealed a molecular link between sulfide and butyrate metabolism, which are known to interact. Three different CoQ₁-bound crystal structures furnished insights into how diverse substrates access human SQR, and provided snapshots of the reaction coordinate. Unexpectedly, the active site cysteines in SQR are configured in a bridging trisulfide at the start and end of the catalytic cycle, and the presence of sulfane sulfur was confirmed biochemic

SUBMITTER: Landry AP 

PROVIDER: S-EPMC6906606 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature