Peroxiredoxin evolution and the regulation of hydrogen peroxide signaling

Science. 2003 Apr 25;300(5619):650-3. doi: 10.1126/science.1080405.

Abstract

Eukaryotic 2-Cys peroxiredoxins (2-Cys Prxs) not only act as antioxidants, but also appear to regulate hydrogen peroxide-mediated signal transduction. We show that bacterial 2-Cys Prxs are much less sensitive to oxidative inactivation than are eukaryotic 2-Cys Prxs. By identifying two sequence motifs unique to the sensitive 2-Cys Prxs and comparing the crystal structure of a bacterial 2-Cys Prx at 2.2 angstrom resolution with other Prx structures, we define the structural origins of sensitivity. We suggest this adaptation allows 2-Cys Prxs to act as floodgates, keeping resting levels of hydrogen peroxide low, while permitting higher levels during signal transduction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Bacteria / enzymology
  • Binding Sites
  • Catalysis
  • Crystallography, X-Ray
  • Cysteine / metabolism
  • Disulfides / chemistry
  • Disulfides / metabolism
  • Evolution, Molecular
  • Humans
  • Hydrogen Peroxide / metabolism*
  • Models, Chemical
  • Models, Molecular
  • Molecular Sequence Data
  • Oxidation-Reduction
  • Peroxidases / chemistry*
  • Peroxidases / metabolism*
  • Peroxiredoxins
  • Protein Conformation
  • Protein Folding
  • Protein Structure, Secondary
  • Salmonella typhimurium / enzymology*
  • Sequence Alignment
  • Signal Transduction*
  • Sulfenic Acids / metabolism
  • Sulfinic Acids / metabolism
  • Yeasts / enzymology

Substances

  • Disulfides
  • Sulfenic Acids
  • Sulfinic Acids
  • Hydrogen Peroxide
  • Peroxidases
  • Peroxiredoxins
  • Cysteine

Associated data

  • PDB/1N8J