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

Nature. 2003 Oct 30;425(6961):980-4. 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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Amino Acid Sequence
  • Binding Sites
  • Cysteine / metabolism*
  • Disulfides / metabolism
  • Gene Expression Regulation, Fungal / drug effects
  • Hydrogen Peroxide / pharmacology
  • Molecular Sequence Data
  • Molecular Weight
  • Neoplasm Proteins*
  • Oxidation-Reduction
  • Oxidoreductases / chemistry
  • Oxidoreductases / genetics
  • Oxidoreductases / metabolism*
  • Oxidoreductases Acting on Sulfur Group Donors
  • Peroxidases / chemistry
  • Peroxidases / metabolism
  • Peroxiredoxins
  • Protein Binding
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sulfinic Acids / metabolism*


  • Disulfides
  • Neoplasm Proteins
  • Saccharomyces cerevisiae Proteins
  • Sulfinic Acids
  • Adenosine Triphosphate
  • Hydrogen Peroxide
  • Oxidoreductases
  • Peroxidases
  • Peroxiredoxins
  • Oxidoreductases Acting on Sulfur Group Donors
  • SRX1 protein, S cerevisiae
  • Cysteine