Yang Jing, Carroll Kate S, Liebler Daniel C
From the ‡National Center for Protein Sciences · Beijing, Beijing, 102206, China; §State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing, 102206, China;
¶Department of Chemistry, The Scripps Research Institute, Jupiter, Florida 33458;
Mol Cell Proteomics. 2016 Jan;15(1):1-11. doi: 10.1074/mcp.O115.056051. Epub 2015 Oct 30.
Cysteine occupies a unique place in protein chemistry. The nucleophilic thiol group allows cysteine to undergo a broad range of redox modifications beyond classical thiol-disulfide redox equilibria, including S-sulfenylation (-SOH), S-sulfinylation (-SO(2)H), S-sulfonylation (-SO(3)H), S-nitrosylation (-SNO), S-sulfhydration (-SSH), S-glutathionylation (-SSG), and others. Emerging evidence suggests that these post-translational modifications (PTM) are important in cellular redox regulation and protection against oxidative damage. Identification of protein targets of thiol redox modifications is crucial to understanding their roles in biology and disease. However, analysis of these highly labile and dynamic modifications poses challenges. Recent advances in the design of probes for thiol redox forms, together with innovative mass spectrometry based chemoproteomics methods make it possible to perform global, site-specific, and quantitative analyses of thiol redox modifications in complex proteomes. Here, we review chemical proteomic strategies used to expand the landscape of thiol redox modifications.
半胱氨酸在蛋白质化学中占据独特地位。亲核硫醇基团使半胱氨酸能够经历一系列超出经典硫醇 - 二硫键氧化还原平衡的氧化还原修饰，包括S - 亚磺酰化（-SOH）、S - 亚磺酰亚胺化（-SO(2)H）、S - 磺酰化（-SO(3)H）、S - 亚硝基化（-SNO）、S - 硫氢化（-SSH）、S - 谷胱甘肽化（-SSG）等。新出现的证据表明，这些翻译后修饰（PTM）在细胞氧化还原调节和抵御氧化损伤方面很重要。鉴定硫醇氧化还原修饰的蛋白质靶点对于理解它们在生物学和疾病中的作用至关重要。然而，分析这些高度不稳定和动态的修饰带来了挑战。硫醇氧化还原形式探针设计的最新进展，以及基于创新质谱的化学蛋白质组学方法，使得对复杂蛋白质组中的硫醇氧化还原修饰进行全局、位点特异性和定量分析成为可能。在此，我们综述用于拓展硫醇氧化还原修饰研究领域的化学蛋白质组学策略。
