Biosynthesis of a central intermediate in hydrogen sulfide metabolism by a novel human sulfurtransferase and its yeast ortholog.

摘要: Human sulfide:quinone oxidoreductase (SQOR) catalyzes the conversion of H2S to thiosulfate, first step in mammalian metabolism. SQOR’s inability produce glutathione persulfide (GSS–) substrate for sulfur dioxygenase (SDO) suggested that a thiosulfate:glutathione sulfurtransferase (TST) was required provide missing link between SQOR and SDO reactions. Although TST could be purified from yeast, attempts isolate enzyme were not successful. We used bioinformatic approaches identify genes likely encode human (TSTD1) its yeast ortholog (RDL1). Recombinant TSTD1 RDL1 catalyze predicted thiosulfate-dependent GSS–. Both enzymes contain rhodanese homology domain single catalytically essential cysteine, which is converted cysteine upon reaction with thiosulfate. GSS– potent inhibitor RDL1, as judged by initial rate accelerations ≥25-fold lower Km values observed t...