title: Peroxiredoxin evolution and the regulation of hydrogen peroxide signaling.
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.
authors.affiliation: Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97333, USA.
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Wood
authors.forename: Leslie B
authors.initials: LB
authors.lastname: Poole
authors.forename: P Andrew
authors.initials: PA
authors.lastname: Karplus
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001419:Bacteria / Q000201:enzymology; D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000378:metabolism; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism; D019143:Evolution, Molecular; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010544:Peroxidases / Q000737:chemistry* / Q000378:metabolism*; D054464:Peroxiredoxins; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012486:Salmonella typhimurium / Q000201:enzymology*; D016415:Sequence Alignment; D015398:Signal Transduction; D013434:Sulfenic Acids / Q000378:metabolism; D013441:Sulfinic Acids / Q000378:metabolism; D015003:Yeasts / Q000201:enzymology
chemical_list: D004220:Disulfides; D013434:Sulfenic Acids; D013441:Sulfinic Acids; D006861:Hydrogen Peroxide; D010544:Peroxidases; D054464:Peroxiredoxins; D003545:Cysteine