title: PDI and glutathione-mediated reduction of the glutathionylated variant of human lysozyme.
abstract: A mutant human lysozyme, designated as C77A-a, in which glutathione is bound to Cys95, has been shown to mimic an intermediate in the formation of a disulfide bond during folding of human (h)-lysozyme. Protein disulfide isomerase (PDI), which is believed to catalyze disulfide bond formation and associated protein folding in the endoplasmic reticulum, attacked the glutathionylated h-lysozyme C77A-a to dissociate the glutathione molecule. Structural analyses showed that the protein is folded and that the structure around the disulfide bond, buried in a hydrophobic core, between the protein and the bound glutathione is fairly rigid. Thioredoxin, which has higher reducing activity of protein disulfides than PDI, catalyzed the reduction with lower efficiency. These results strongly suggest that PDI can catalyze the disulfide formation in intermediates with compact structure like the native states in the later step of in vivo protein folding.
authors.affiliation: Protein Engineering Research Institute, Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hayano
authors.forename: K
authors.initials: K
authors.lastname: Inaka
authors.forename: M
authors.initials: M
authors.lastname: Otsu
authors.forename: Y
authors.initials: Y
authors.lastname: Taniyama
authors.forename: K
authors.initials: K
authors.lastname: Miki
authors.forename: M
authors.initials: M
authors.lastname: Matsushima
authors.forename: M
authors.initials: M
authors.lastname: Kikuchi
mesh_terms: D000818:Animals; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000378:metabolism; D004220:Disulfides; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D007535:Isomerases / Q000378:metabolism*; D009113:Muramidase / Q000378:metabolism*; D010084:Oxidation-Reduction; D019704:Protein Disulfide-Isomerases; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D013379:Substrate Specificity; D013879:Thioredoxins / Q000378:metabolism
chemical_list: D004220:Disulfides; D013879:Thioredoxins; D009113:Muramidase; D007535:Isomerases; D019704:Protein Disulfide-Isomerases; D005978:Glutathione; D003545:Cysteine