title: An amphiphilic selenide catalyst behaves like a hybrid mimic of protein disulfide isomerase and glutathione peroxidase 7.
abstract: Protein disulfide isomerase (PDI) and glutathione peroxidase 7 (GPx7) cooperatively promote the oxidative folding of disulfide (SS)-containing proteins in endoplasmic reticulum by recognizing the nascent proteins to convert them into the native folds by means of SS formation and SS isomerization and by catalyzing reoxidation of reduced PDI with H2O2, respectively. In this study, new amphiphilic selenides with a long-chain alkyl group were designed as hybrid mimics of PDI and GPx7 and were applied to the refolding of reduced hen egg-white lysozyme (HEL-R). Competitive SS formation at pH 4 using HEL-R and glutathione (GSH) in the presence of the selenide catalyst and H2O2 showed that the amphiphilic selenides can preferentially catalyze SS formation of HEL-R, probably on account of hydrophobic interactions between the protein and the catalyst. In contrast, simple water-soluble selenides did not exhibit such behavior. In addition, when the pH of the solution was adjusted to 8.5 after the SS formation, surviving GSH promoted the SS isomerization of misfolded HEL to recover the native SS linkages. Thus, the amphiphilic selenides designed here could mimic the function of the PDI-GPx7 system. The combination of a water-soluble selenide and a long-chain alkyl group would be a useful motif in designing medicines for both protein misfolding diseases and antioxidant therapy.
authors.affiliation: Department of Chemistry, School of Science, Tokai University, Kitakaname, Hiratsuka-shi, Kanagawa 259-1292 (Japan).
authors.forename: Kenta
authors.initials: K
authors.lastname: Arai
authors.forename: Kenji
authors.initials: K
authors.lastname: Moriai
authors.forename: Akinobu
authors.initials: A
authors.lastname: Ogawa
authors.forename: Michio
authors.initials: M
authors.lastname: Iwaoka
mesh_terms: D040761:Biomimetic Materials / Q000737:chemistry* / Q000378:metabolism; D002384:Catalysis; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism; D005979:Glutathione Peroxidase; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000378:metabolism; D008968:Molecular Conformation; D016566:Organoselenium Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D010544:Peroxidases / Q000737:chemistry* / Q000378:metabolism; D019704:Protein Disulfide-Isomerases / Q000737:chemistry* / Q000378:metabolism; D013501:Surface-Active Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism
chemical_list: D004220:Disulfides; D016566:Organoselenium Compounds; D013501:Surface-Active Agents; D006861:Hydrogen Peroxide; D010544:Peroxidases; C558641:GPX7 protein, human; D005979:Glutathione Peroxidase; D019704:Protein Disulfide-Isomerases
keywords: amphiphiles; antioxidants; enzyme models; protein folding; selenides