ATP-dependent reduction of cysteine-sulphinic acid by S. cerevisiae sulphiredoxin.
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 M(r) = 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.
Laboratoire Stress Oxydants et Cancer, SBGM, DBJC, CEA-Saclay, 91191 Gif-sur-Yvette cedex, France.
Benoît
B
Biteau
Jean
J
Labarre
Michel B
MB
Toledano
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000595:Amino Acid Sequence; D001665:Binding Sites; D003545:Cysteine / Q000378:metabolism*; D004220:Disulfides / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009363:Neoplasm Proteins; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050862:Oxidoreductases Acting on Sulfur Group Donors; D010544:Peroxidases / Q000737:chemistry / Q000378:metabolism; D054464:Peroxiredoxins; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013441:Sulfinic Acids / Q000378:metabolism*
D004220:Disulfides; D009363:Neoplasm Proteins; D029701:Saccharomyces cerevisiae Proteins; D013441:Sulfinic Acids; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D010088:Oxidoreductases; D010544:Peroxidases; D054464:Peroxiredoxins; D050862:Oxidoreductases Acting on Sulfur Group Donors; C479426:SRX1 protein, S cerevisiae; D003545:Cysteine