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Post-translational modification by cysteine protects Cu/Zn-superoxide dismutase from oxidative damage

Auclair, JR and Johnson, JL and Liu, Q and Salisbury, JP and Rotunno, MS and Petsko, GA and Ringe, D and Brown, J and Bosco, DA and Agar, JN (2013) Post-translational modification by cysteine protects Cu/Zn-superoxide dismutase from oxidative damage. Biochemistry. pp. 6137-6144.

Abstract

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, Cys<sub>111</sub>. 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. 2013 American Chemical Society

Item Type: Article
Additional Information: pubid: 176 nvp_institute: NIBR contributor_address: (Auclair, Johnson, Liu, Salisbury, Petsko, Ringe, Agar) Departments of Biochemistry and Chemistry, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02454, United States (Rotunno, Brown Jr., Bosco) Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01655, United States (Bosco) Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01655, United States (Auclair, Salisbury, Agar) Department of Chemistry and Chemical Biology and Pharmaceutical Sciences, Barnett Institute, Northeastern University, Boston, MA 02115, United States (Johnson) Novartis Institute for Biomedical Research, Cambridge, MA 02139, United States
Date Deposited: 13 Oct 2015 13:12
Last Modified: 13 Oct 2015 13:12
URI: https://oak.novartis.com/id/eprint/21999

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