title: Sestrin 2 is not a reductase for cysteine sulfinic acid of peroxiredoxins.
abstract: The active-site cysteine of 2-Cys peroxiredoxins (Prxs), a subgroup of the Prx family, is reversibly hyperoxidized to cysteine sulfinic acid during catalysis with concomitant loss of peroxidase activity. The reduction of sulfinic 2-Cys Prx enzymes, the first known biologic of such a reaction, has been reported to be catalyzed by either sulfiredoxin (Srx) or sestrin (Sesn) 2. The 13-kDa Srx and 60-kDa Sesn 2 show no sequence similarity, however. Whereas the reductase function of Srx has been confirmed by several studies, such is not the case for Sesn 2. We have now shown that (a) recombinant Sesn 2 did not catalyze the reduction of sulfinic Prx I in vitro, whereas Srx did; (b) overexpression of Sesn 2 in HeLa or A549 cells did not affect the reduction of 2-Cys Prxs, whereas overexpression of Srx markedly increased the reduction rate; and (c) the rate of sulfinic 2-Cys Prx reduction in embryonic fibroblasts derived from Sesn 2-knockout mice did not differ from that in those derived from wild-type mice. These results suggest that, unlike Srx, Sesn 2 is not a sulfinic Prx reductase.
authors.affiliation: Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea.
authors.forename: Hyun Ae
authors.initials: HA
authors.lastname: Woo
authors.forename: Soo Han
authors.initials: SH
authors.lastname: Bae
authors.forename: Sunjoo
authors.initials: S
authors.lastname: Park
authors.forename: Sue Goo
authors.initials: SG
authors.lastname: Rhee
mesh_terms: D000818:Animals; D055162:Biocatalysis; D002460:Cell Line; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000378:metabolism*; D054464:Peroxiredoxins / Q000378:metabolism*; D000084622:Sestrins
chemical_list: D003545:Cysteine; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D009687:Nuclear Proteins; D054464:Peroxiredoxins; C465398:SESN2 protein, human; D000084622:Sestrins; C013461:cysteine sulfinic acid