6wh6
From Proteopedia
Crystal structure of human sulfide quinone oxidoreductase in complex with coenzyme Q (cyanide soaked)
Structural highlights
FunctionSQOR_HUMAN Catalyzes the oxidation of hydrogen sulfide with the help of a quinone, such as ubiquinone, giving rise to thiosulfate and ultimately to sulfane (molecular sulfur) atoms. Requires an additional electron acceptor; can use sulfite, sulfide or cyanide (in vitro).[1] Publication Abstract from PubMedSulfide quinone oxidoreductase (SQOR) catalyzes the first step in sulfide clearance, coupling H2S oxidation to coenzyme Q reduction. Recent structures of human SQOR revealed a sulfur atom bridging the SQOR active site cysteines in a trisulfide configuration. Here, we assessed the importance of this cofactor using kinetic, crystallographic, and computational modeling approaches. Cyanolysis of SQOR proceeds via formation of an intense charge transfer complex that subsequently decays to eliminate thiocyanate. We captured a disulfanyl-methanimido thioate intermediate in the SQOR crystal structure, revealing how cyanolysis leads to reversible loss of SQOR activity that is restored in the presence of sulfide. Computational modeling and MD simulations revealed an approximately 10(5)-fold rate enhancement for nucleophilic addition of sulfide into the trisulfide versus a disulfide cofactor. The cysteine trisulfide in SQOR is thus critical for activity and provides a significant catalytic advantage over a cysteine disulfide. Dismantling and Rebuilding the Trisulfide Cofactor Demonstrates Its Essential Role in Human Sulfide Quinone Oxidoreductase.,Landry AP, Moon S, Bonanata J, Cho US, Coitino EL, Banerjee R J Am Chem Soc. 2020 Aug 19;142(33):14295-14306. doi: 10.1021/jacs.0c06066. Epub, 2020 Aug 10. PMID:32787249[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
