Hydrogen Sulfide Oxidation by Sulfide Quinone Oxidoreductase.

Hydrogen Sulfide Oxidation by Sulfide Quinone Oxidoreductase.
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DOI:
10.1002/cbic.202000661
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发表时间:
2021-03-16
期刊:
Chembiochem : a European journal of chemical biology
影响因子:
--
通讯作者:
Banerjee R
Banerjee R
中科院分区:
其他
文献类型:
--
作者:
Landry AP;Ballou DP;Banerjee R

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硫化氢 (H2S) 是一种环境毒素,也是古代微生物代谢的遗产,作为神经调节剂的发现激发了人们新的兴趣。虽然许多生理反应归因于低 H2S 水平,但较高水平会抑制电子传递链中的复合物 IV。为了防止呼吸道中毒,存在一组包含线粒体硫化物氧化途径的专用酶来清除 H2S。该途径中的关键步骤由硫化物醌氧化还原酶 (SQOR) 催化,该酶将电子传递链中的硫化物氧化与辅酶 Q10 还原偶联。 SQOR 反应可防止 H2S 积聚并生成高反应性的过硫化物产物,这些产物可进一步氧化或通过过硫化作用修饰蛋白​​质中的半胱氨酸残基。在这里,我们回顾了人类 SQOR 的动力学和结构特征,以及其非常规的氧化还原辅因子配置和底物混杂性如何导致硫化物清除并可能扩大 H2S 的信号传导潜力。 SQOR 的这种双重作用使其成为基于 H2S 的治疗的有希望的目标。调节硫化物毒性和信号传导:人硫化物醌氧化还原酶利用活性位点半胱氨酸三硫化物来解毒硫化氢(一种呼吸道毒物)。在此,我们详细介绍了硫化物醌氧化还原酶的显着酶学及其对硫化物信号传导的潜在调节。
Hydrogen sulfide (H2S) is an environmental toxin and a heritage of ancient microbial metabolism, which has stimulated new interest following its discovery as a neuromodulator. While many physiological responses have been attributed to low H2S levels, higher levels inhibit complex IV in the electron transport chain. To prevent respiratory poisoning, a dedicated set of enzymes comprising the mitochondrial sulfide oxidation pathway exists to clear H2S. The committed step in this pathway is catalyzed by sulfide quinone oxidoreductase (SQOR), which couples sulfide oxidation to coenzyme Q10 reduction in the electron transport chain. The SQOR reaction prevents H2S accumulation and generates highly reactive persulfide species as products, which can be further oxidized or can modify cysteine residues in proteins via persulfidation. Here, we review the kinetic, and structural characteristics of human SQOR, and how its unconventional redox cofactor configuration and substrate promiscuity lead to sulfide clearance and potentially expand the signaling potential of H2S. This dual role of SQOR makes it a promising target for H2S-based therapeutics. Regulating sulfide toxicity and signaling: Utilizing an active site cysteine trisulfide, human sulfide quinone oxidoreductase detoxifies hydrogen sulfide, a respiratory poison. Herein, we detail the remarkable enzymology of sulfide quinone oxidoreductase and its potential modulation of sulfide signaling.
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