Post-Translational Modification by Cysteine Protects Cu/Zn-Superoxide Dismutase from Oxidative Damage

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• 作者：Jared R. Auclair ; Joshua L. Johnson ; Qian Liu ; Joseph P. Salisbury ; Melissa S. Rotunno ; Gregory A. Petsko ; Dagmar Ringe ; Robert H. Brown ; Jr. ; Daryl A. Bosco ; Jeffrey N. Agar
• 刊名：Biochemistry
• 出版年：2013
• 出版时间：September 10, 2013
• 年：2013
• 卷：52
• 期：36
• 页码：6137-6144
• 全文大小：360K
• 年卷期：v.52,no.36(September 10, 2013)
• ISSN：1520-4995

文摘

Reactive oxygen species (ROS) are cytotoxic. To remove ROS, cells have developed ROS-specific defense mechanisms, including the enzyme Cu/Zn superoxide dismutase (SOD1), which catalyzes the disproportionation of superoxide anions into molecular oxygen and hydrogen peroxide. Although hydrogen peroxide is less reactive than superoxide, it is still capable of oxidizing, unfolding, and inactivating SOD1, at least in vitro. To explore the relevance of post-translational modification (PTM) of SOD1, including peroxide-related modifications, SOD1 was purified from postmortem human nervous tissue. As much as half of all purified SOD1 protein contained non-native post-translational modifications (PTMs), the most prevalent modifications being cysteinylation and peroxide-related oxidations. Many PTMs targeted a single reactive SOD1 cysteine, Cys₁₁₁. An intriguing observation was that unlike native SOD1, cysteinylated SOD1 was not oxidized. To further characterize how cysteinylation may protect SOD1 from oxidation, cysteine-modified SOD1 was prepared in vitro and exposed to peroxide. Cysteinylation conferred nearly complete protection from peroxide-induced oxidation of SOD1. Moreover, SOD1 that has been cysteinylated and peroxide oxidized in vitro comprised a set of PTMs that bear a striking resemblance to the myriad of PTMs observed in SOD1 purified from human tissue.