title: Contribution of selenocysteine to the peroxidase activity of selenoprotein S.
abstract: Selenoprotein S (SelS, VIMP) is an intrinsically disordered enzyme that utilizes selenocysteine to catalyze the reduction of disulfide bonds and peroxides. Here it is demonstrated that selenocysteine is the residue oxidized by the peroxide substrate. It is possible to trap the reaction intermediate selenenic acid when the resolving cysteine is mutated. The selenocysteine allows SelS to rapidly re-form its selenenylsulfide bond following its reduction, and to resist inactivation by H2O2. We propose that SelS's peroxidase mechanism is similar to that of atypical 2-Cys peroxiredoxin and that selenocysteine allows SelS to sustain activity under oxidative stress.
authors.affiliation: Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Sharon
authors.initials: S
authors.lastname: Rozovsky
mesh_terms: D055162:Biocatalysis; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008956:Models, Chemical; D009154:Mutation; D009195:Peroxidase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017279:Selenocysteine / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051140:Selenoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D013379:Substrate Specificity; D013880:Thioredoxin-Disulfide Reductase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; C487710:SELENOS protein, human; D051140:Selenoproteins; D017279:Selenocysteine; D006861:Hydrogen Peroxide; D009195:Peroxidase; D013880:Thioredoxin-Disulfide Reductase
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