Polymorphic Variants of Human Rhodanese Exhibit Differences in Thermal Stability and Sulfur Transfer Kinetics.

摘要: Rhodanese is a component of the mitochondrial H2S oxidation pathway. catalyzes transfer sulfane sulfur from glutathione persulfide (GSSH) to sulfite generating thiosulfate and cyanide thiocyanate. Two polymorphic variations have been identified in rhodanese coding sequence French Caucasian population. The first, 306A→C, has an allelic frequency 1% results E102D substitution encoded protein. second polymorphism, 853C→G, 5% leads P285A substitution. In this study, we examined differences stability between wild-type variants kinetics reactions. Asp-102 Ala-285 are more stable than exhibit kcat/Km,CN values that 17- 1.6-fold higher, respectively. All three forms preferentially catalyze GSSH sulfite, glutathione. kcat/Km,sulfite for reaction were 1.6- (Asp-102) 4-fold (Ala-285) lower rhodanese, whereas kcat/Km,GSSH similar all enzymes. Thiosulfate-dependent production murine liver lysate low, consistent with role sulfide oxidation. Our studies show distant active site differentially modulate sulfurtransferase activity human versus might be important susceptibility diseases where dysfunction implicated, e.g. inflammatory bowel diseases.