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A Catalytic Trisulfide in Human Sulfide Quinone Oxidoreductase Catalyzes Coenzyme A Persulfide Synthesis and Inhibits Butyrate Oxidation.
Cell Chemical Biology ( IF 8.6 ) Pub Date : 2019-10-04 , DOI: 10.1016/j.chembiol.2019.09.010
Aaron P Landry 1 , Sojin Moon 1 , Hanseong Kim 1 , Pramod K Yadav 1 , Arkajit Guha 1 , Uhn-Soo Cho 1 , Ruma Banerjee 1
Affiliation  

Mitochondrial sulfide quinone oxidoreductase (SQR) catalyzes the oxidation of H2S to glutathione persulfide with concomitant reduction of CoQ10. We report herein that the promiscuous activity of human SQR supported the conversion of CoA to CoA-SSH (CoA-persulfide), a potent inhibitor of butyryl-CoA dehydrogenase, and revealed a molecular link between sulfide and butyrate metabolism, which are known to interact. Three different CoQ1-bound crystal structures furnished insights into how diverse substrates access human SQR, and provided snapshots of the reaction coordinate. Unexpectedly, the active site cysteines in SQR are configured in a bridging trisulfide at the start and end of the catalytic cycle, and the presence of sulfane sulfur was confirmed biochemically. Importantly, our study leads to a mechanistic proposal for human SQR in which sulfide addition to the trisulfide cofactor eliminates 201Cys-SSH, forming an intense charge-transfer complex with flavin adenine dinucleotide, and 379Cys-SSH, which transfers sulfur to an external acceptor.

中文翻译:

人硫化物醌醌氧化还原酶中的催化三硫化物催化辅酶A过硫化物的合成并抑制丁酸的氧化。

线粒体硫化物醌氧化还原酶(SQR)催化H2S氧化为谷胱甘肽过硫化物,同时还原CoQ10。我们在此报告,人类SQR的混杂活动支持CoA向CoA-SSH(CoA-persulfide)(一种丁酰CoA脱氢酶的强效抑制剂)的转化,并揭示了硫化物与丁酸酯代谢之间的分子联系,已知该相互作用。三种不同的与CoQ1结合的晶体结构提供了洞察力,以了解各种底物如何访问人类SQR,并提供了反应坐标的快照。出乎意料的是,在催化循环的开始和结束时,SQR中的活性位点半胱氨酸被配置为桥联的三硫化物,并且通过化学方法确定了硫烷硫的存在。重要的,
更新日期:2019-11-09
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