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Thiosulfate:glutathione sulfurtransferase (TSTD1) is a human enzyme of the sulfurtransferase superfamily, primarily characterized by a single rhodanese-like domain and located in the cytosol. TSTD1 catalyzes the transfer of sulfur from thiosulfate to glutathione, forming S-sulfanylglutathione (GSS–), which acts as a reactive intermediate in hydrogen sulfide (H₂S) metabolism. TSTD1 serves as a crucial link between hydrogen sulfide oxidation by sulfide:quinone oxidoreductase (SQOR) and subsequent metabolism by sulfur dioxygenase (SDO) in mitochondria. The enzyme exhibits highest activity with thioredoxin as a sulfane sulfur acceptor but only moderate efficiency with thiosulfate as a donor. TSTD1’s open active site distinguishes it structurally from other known sulfurtransferases. Expression of TSTD1 has been documented in various tissues and is notably higher at the apical surface of human colonic crypts, interacting with sulfide-releasing microbes. Its overexpression in colon cancer suggests a potential role in tumor biology or as a biomarker, although definitive disease associations require further clinical validation. No approved drugs currently target TSTD1 directly, and its full physiological and pathological significance is still being elucidated.
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