3-mercaptopyruvate sulfurtransferase (MPST)

3-Mercaptopyruvate sulfurtransferase (MPST) is a cytoplasmic enzyme (EC 2.8.1.2) belonging to the rhodanese family of sulfurtransferases, catalyzing the transfer of sulfane sulfur from 3-mercaptopyruvate to acceptors like cyanide or thiols, forming pyruvate and products such as thiocyanate or hydrogen sulfide (H2S). It operates via a double-displacement mechanism involving a catalytic cysteine persulfide intermediate (Cys247 in humans), supported by a Ser-His-Asp triad, and contributes to cysteine degradation, tRNA thiolation, protein urmylation, and cyanide detoxification. MPST is broadly expressed in tissues including liver, kidney, heart, brain, and vasculature, where it generates H2S to modulate nitric oxide signaling and promote vasodilation. Dysregulation links it to oxidative stress resistance, mitochondrial function, fatty acid metabolism, and aging-related changes. In disease, elevated MPST correlates with bladder cancer progression, serving as a potential biomarker, while deficiency causes mercaptolactate-cysteine disulfiduria (Ampola syndrome) with neurological symptoms; it also influences intestinal apoptosis and metabolic disorders. Though not a primary drug target, selective inhibitors targeting its persulfide site have been characterized for H2S modulation research.

Other names

3-mercaptopyruvate:cyanide sulfurtransferasebeta-mercaptopyruvate sulfurtransferasemercaptopyruvate sulfurtransferase

Inhibition of persulfide formation at catalytic cysteine (Cys247/Cys253); Double displacement via enzyme-bound persulfide intermediate