Protein-sulfenic acids: Diverse roles for an unlikely player in enzyme catalysis and redox regulation
Protein-sulfenic acids: Diverse roles for an unlikely player in enzyme catalysis and redox regulation
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DOI：
10.1021/bi992025k
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发表时间：
1999-11-23
期刊：
影响因子：
2.9
通讯作者：
Parsonage, D
中科院分区：
文献类型：
--
作者：
Claiborne, A;Yeh, JI;Parsonage, D
虽然 20 多年来人们就知道异常稳定的半胱氨酸-磺酸 (Cys-SOH) 衍生物可以通过温和氧化引入选定的蛋白质中，但直到最近才出现功能性 Cys-SOH 与天然蛋白质（例如 NADH 过氧化物酶和 NADH 氧化酶、腈水合酶以及 hORF6 和 AhpC 过氧化还原酶）的化学和晶体学证据。此外，Cys-SOH 形式的蛋白质酪氨酸磷酸酶和谷胱甘肽还原酶被认为分别在酪氨酸磷酸化依赖性信号转导事件和亚硝化应激期间对这些酶的可逆抑制中发挥关键作用。还提供了大量的化学数据，表明Cys-SOH参与转录因子如Fos和Jun（激活蛋白-1）和牛乳头瘤病毒-1 E2蛋白的氧化还原调节。从功能上讲，NADH 过氧化物酶、NADH 氧化酶和过氧化还原蛋白中的 Cys-SOH 在过氧化物还原过程中充当催化必需的氧化还原中心或瞬时中间体。在腈水合酶中，活性位点 Cys-SOH 在铁配位和 NO 结合中发挥作用，但不发挥任何催化氧化还原作用。另一方面，在 Fos 和 Jun 以及 E2 蛋白中，关键的 Cys-SH 充当细胞内氧化还原状态的传感器；所提出的 Cys-SOH 可逆氧化会抑制相应的 DNA 结合活性。这些功能性 Cys-SOH 在多种细胞过程中发挥作用，包括信号转导、氧代谢和氧化应激反应、转录调节以及丙烯酰胺的工业生产，它们的详细分析开始为了解蛋白质-SOH 稳定性和功能提供必要的化学基础。
While it has been known for more than 20 years that unusually stable cysteine-sulfenic acid (Cys-SOH) derivatives can be introduced in selected proteins by mild oxidation, only recently have chemical and crystallographic evidence for functional Cys-SOH been presented with native proteins such as NADH peroxidase and NADH oxidase, nitrile hydratase, and the hORF6 and AhpC peroxiredoxins, In addition, Cys-SOH forms of protein tyrosine phosphatases and glutathione reductase have been suggested to play key roles in the reversible inhibition of these enzymes during tyrosine phosphorylation-dependent signal transduction events and nitrosative stress, respectively, Substantial chemical data have also been presented which implicate Cys-SOH in redox regulation of transcription factors such as Fos and Jun (activator protein-1) and bovine papillomavirus-l E2 protein. Functionally, the Cys-SOHs in NADH peroxidase, NADH oxidase, and the peroxiredoxins serve as either catalytically essential redox centers or transient intermediates during peroxide reduction, In nitrile hydratase, the active-site Cys-SOH functions in both iron coordination and NO binding but does not play any catalytic redox role. In Fos and Jun and the E2 protein, on the other hand, a key Cys-SH serves as a sensor for intracellular redox status; reversible oxidation to Cys-SOH as proposed inhibits the corresponding DNA binding activity. These functional Cys-SOHs have roles in diverse cellular processes, including signal transduction, oxygen metabolism and the oxidative stress response, and transcriptional regulation, as well as in the industrial production of acrylamide, and their detailed analyses are beginning to provide the chemical foundation necessary for understanding protein-SOH stabilization and function.