X-Ray Structure of Human Sulfide:Quinone Oxidoreductase: Insights into the Mechanism of Mitochondrial Hydrogen Sulfide Oxidation.,Structure

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X-Ray Structure of Human Sulfide:Quinone Oxidoreductase: Insights into the Mechanism of Mitochondrial Hydrogen Sulfide Oxidation.
Structure ( IF 4.4 ) Pub Date : 2019-03-21 , DOI: 10.1016/j.str.2019.03.002
Michael R Jackson ₁ , Patrick J Loll ₁ , Marilyn Schuman Jorns ₁

Affiliation

Hydrogen sulfide (H2S) is a gasotransmitter exhibiting pivotal functions in diverse biological processes, including activation of multiple cardioprotective pathways. Sulfide:quinone oxidoreductase (SQOR) is an integral membrane flavoprotein that catalyzes the first step in the mitochondrial metabolism of H2S. As such, it plays a critical role in controlling physiological levels of the gasotransmitter and has attracted keen interest as a potential drug target. We report the crystal structure of human SQOR, unraveling the molecular basis for the enzyme's ability to catalyze sulfane sulfur transfer reactions with structurally diverse acceptors. We demonstrate that human SQOR contains unique features: an electropositive surface depression implicated as a binding site for sulfane sulfur acceptors and postulated to funnel negatively charged substrates to a hydrophilic H2S-oxidizing active site, which is connected to a hydrophobic internal tunnel that binds coenzyme Q. These findings support a proposed model for catalysis and open the door for structure-based drug design.

中文翻译：

人类硫化物的X射线结构：奎宁氧化还原酶：线粒体硫化氢氧化机理的见解。

硫化氢（H2S）是一种气体递质，在多种生物过程中发挥关键作用，包括激活多个心脏保护途径。硫化物：醌氧化还原酶（SQOR）是一种不可或缺的膜黄素蛋白，可催化H2S线粒体代谢的第一步。因此，它在控制气体传输剂的生理水平中起着至关重要的作用，并且作为潜在的药物靶标引起了人们的浓厚兴趣。我们报告了人类SQOR的晶体结构，揭示了该酶催化具有结构多样的受体的硫磺硫转移反应的能力的分子基础。我们证明人类SQOR包含独特的功能：

更新日期：2019-05-16

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