title: Reduction of cysteine sulfinic acid by sulfiredoxin is specific to 2-cys peroxiredoxins.
abstract: Cysteine residues of certain peroxiredoxins (Prxs) undergo reversible oxidation to sulfinic acid (Cys-SO2H) and the reduction reaction is catalyzed by sulfiredoxin (Srx). Specific Cys residues of various other proteins are also oxidized to sulfinic acid, suggesting that formation of Cys-SO2H might be a novel posttranslational modification that contributes to regulation of protein function. To examine the susceptibility of sulfinic forms of proteins to reduction by Srx, we prepared such forms of all six mammalian Prx isoforms and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Purified sulfiredoxin reduced the sulfinic forms of the four 2-Cys members (Prx I to Prx IV) of the Prx family in vitro, but it did not affect those of Prx V, Prx VI, or GAPDH. Furthermore, Srx bound specifically to the four 2-Cys Prxs in vitro and in cells. Sulfinic forms of Prx I and Prx II, but not of Prx VI or GAPDH, present in H2O2-treated A549 cells were gradually reduced after removal of H2O2; overexpression of Srx increased the rate of the reduction of Prx I and Prx II but did not induce that of Prx VI or GAPDH. These results suggest that reduction of Cys-SO2H by Srx is specific to 2-Cys Prx isoforms. For proteins such as Prx VI and GAPDH, sulfinic acid formation might be an irreversible process that causes protein damage.
authors.affiliation: Laboratory of Cell Signaling and Laboratory of Biophysical Chemistry, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Hyun Ae
authors.initials: HA
authors.lastname: Woo
authors.forename: Woojin
authors.initials: W
authors.lastname: Jeong
authors.forename: Tong-Shin
authors.initials: TS
authors.lastname: Chang
authors.forename: Kwang Joo
authors.initials: KJ
authors.lastname: Park
authors.forename: Sung Jun
authors.initials: SJ
authors.lastname: Park
authors.forename: Jeong Soo
authors.initials: JS
authors.lastname: Yang
authors.forename: Sue Goo
authors.initials: SG
authors.lastname: Rhee
mesh_terms: D000818:Animals; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism*; D050862:Oxidoreductases Acting on Sulfur Group Donors; D010544:Peroxidases / Q000235:genetics / Q000378:metabolism*; D054465:Peroxiredoxin VI; D054464:Peroxiredoxins; D011499:Protein Processing, Post-Translational / Q000502:physiology; D051381:Rats; D029701:Saccharomyces cerevisiae Proteins; D013379:Substrate Specificity
chemical_list: D007527:Isoenzymes; D029701:Saccharomyces cerevisiae Proteins; D010088:Oxidoreductases; D010544:Peroxidases; D054465:Peroxiredoxin VI; D054464:Peroxiredoxins; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D050862:Oxidoreductases Acting on Sulfur Group Donors; C479426:SRX1 protein, S cerevisiae; D003545:Cysteine; C013461:cysteine sulfinic acid