Wani Revati, Murray Brion W
Oncology Research Unit, Pfizer Worldwide Research and Development, 10770 Science Center Drive, San Diego, CA, 92121, USA.
Methods Mol Biol. 2017;1558:191-212. doi: 10.1007/978-1-4939-6783-4_9.
Reversible cysteine oxidation is an emerging class of protein post-translational modification (PTM) that regulates catalytic activity, modulates conformation, impacts protein-protein interactions, and affects subcellular trafficking of numerous proteins. Redox PTMs encompass a broad array of cysteine oxidation reactions with different half-lives, topographies, and reactivities such as S-glutathionylation and sulfoxidation. Recent studies from our group underscore the lesser known effect of redox protein modifications on drug binding. To date, biological studies to understand mechanistic and functional aspects of redox regulation are technically challenging. A prominent issue is the lack of tools for labeling proteins oxidized to select chemotype/oxidant species in cells. Predictive computational tools and curated databases of oxidized proteins are facilitating structural and functional insights into regulation of the network of oxidized proteins or redox proteome. In this chapter, we discuss analytical platforms for studying protein oxidation, suggest computational tools currently available in the field to determine redox sensitive proteins, and begin to illuminate roles of cysteine redox PTMs in drug pharmacology.
可逆的半胱氨酸氧化是一类新兴的蛋白质翻译后修饰（PTM），它调节催化活性、调节构象、影响蛋白质-蛋白质相互作用，并影响众多蛋白质的亚细胞运输。氧化还原PTM包括一系列具有不同半衰期、拓扑结构和反应性的半胱氨酸氧化反应，如S-谷胱甘肽化和亚砜化。我们小组最近的研究强调了氧化还原蛋白修饰对药物结合的鲜为人知的影响。迄今为止，了解氧化还原调节的机制和功能方面的生物学研究在技术上具有挑战性。一个突出的问题是缺乏用于标记细胞中氧化为特定化学类型/氧化剂种类的蛋白质的工具。预测性计算工具和经过整理的氧化蛋白数据库有助于对氧化蛋白网络或氧化还原蛋白质组的调节进行结构和功能方面的深入了解。在本章中，我们讨论了研究蛋白质氧化的分析平台，介绍了该领域目前可用于确定氧化还原敏感蛋白的计算工具，并开始阐明半胱氨酸氧化还原PTM在药物药理学中的作用。
