ATP-dependent reduction of cysteine-sulphinic acid by S. cerevisiae sulphiredoxin

• Published in: Nature Vol. 425; no. 6961; pp. 980 - 984
• Main Authors: Toledano, Michel B, Biteau, Benoît, Labarre, Jean
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 30.10.2003; Nature Publishing Group
• Subjects: Adenosine Triphosphate - metabolism; Amino Acid Sequence; Binding Sites; Biological and medical sciences; Calcium; Cysteine - metabolism; Disulfides - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Fungal - drug effects; Growth, nutrition, metabolism, transports, enzymes. Molecular biology; Hydrogen Peroxide - pharmacology; Ions; Microbiology; Mineralization; Molecular Sequence Data; Molecular Weight; Mycology; Neoplasm Proteins; Oxidation-Reduction; Oxidoreductases - chemistry; Oxidoreductases - genetics; Oxidoreductases - metabolism; Oxidoreductases Acting on Sulfur Group Donors; Peroxidases - chemistry; Peroxidases - metabolism; Peroxiredoxins; Protein Binding; Proteins; Saccharomyces cerevisiae - chemistry; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - chemistry; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Sulfinic Acids - metabolism; Yeast; Fungi; Cysteine; Reduction; Yeast; Ascomycetes; Antioxidant; ATP; Saccharomyces cerevisiae; Thallophyta
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature02075

Proteins contain thiol-bearing cysteine residues that are sensitive to oxidation, and this may interfere with biological function either as 'damage' or in the context of oxidant-dependent signal transduction. Cysteine thiols oxidized to sulphenic acid are generally unstable, either forming a disulphide with a nearby thiol or being further oxidized to a stable sulphinic acid. Cysteine-sulphenic acids and disulphides are known to be reduced by glutathione or thioredoxin in biological systems, but cysteine-sulphinic acid derivatives have been viewed as irreversible protein modifications. Here we identify a yeast protein of relative molecular mass Mr = 13,000, which we have named sulphiredoxin (identified by the US spelling 'sulfiredoxin', in the Saccharomyces Genome Database), that is conserved in higher eukaryotes and reduces cysteine-sulphinic acid in the yeast peroxiredoxin Tsa1. Peroxiredoxins are ubiquitous thiol-containing antioxidants that reduce hydroperoxides and control hydroperoxide-mediated signalling in mammals. The reduction reaction catalysed by sulphiredoxin requires ATP hydrolysis and magnesium, involving a conserved active-site cysteine residue which forms a transient disulphide linkage with Tsa1. We propose that reduction of cysteine-sulphinic acids by sulphiredoxin involves activation by phosphorylation followed by a thiol-mediated reduction step. Sulphiredoxin is important for the antioxidant function of peroxiredoxins, and is likely to be involved in the repair of proteins containing cysteine-sulphinic acid modifications, and in signalling pathways involving protein oxidation.