title: Redox-active cyclic bis(cysteinyl)peptides as catalysts for in vitro oxidative protein folding.
abstract: The active-site hexapeptides of glutaredoxin (Grx), thioredoxin (Trx), protein disulfide isomerase (PDI), and thioredoxin-reductase (Trr) containing the common motif Cys-Xaa-Yaa-Cys were conformationally restricted by backbone cyclization, and their redox potentials were found to increase in the rank order of Trr < Grx < Trx < PDI peptide, with E'(0) values ranging between -204 mV and -130 mV. In each peptide the thiol pK(a) of one Cys residue was found to be lower than the other (e.g., 7.3 against 9.6 in the PDI peptide). Both the yield and rate of refolding of reduced RNase A in the presence of the bis(cysteinyl)peptides increased with the oxidizing character of the cyclic compounds. These results show that small peptides can function as adjuvants for the in vitro oxidative folding of proteins.
authors.affiliation: Max-Planck-Institute of Biochemistry, 82152, Martinsried, Germany.
authors.forename: Chiara
authors.initials: C
authors.lastname: Cabrele
authors.forename: Stella
authors.initials: S
authors.lastname: Fiori
authors.forename: Stefano
authors.initials: S
authors.lastname: Pegoraro
authors.forename: Luis
authors.initials: L
authors.lastname: Moroder
mesh_terms: D000595:Amino Acid Sequence; D002384:Catalysis; D003545:Cysteine / Q000737:chemistry*; D054477:Glutaredoxins; D007700:Kinetics; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010088:Oxidoreductases; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D019704:Protein Disulfide-Isomerases / Q000737:chemistry / Q000378:metabolism; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D013880:Thioredoxin-Disulfide Reductase / Q000737:chemistry / Q000378:metabolism; D013879:Thioredoxins / Q000737:chemistry / Q000378:metabolism
chemical_list: D054477:Glutaredoxins; D010456:Peptides, Cyclic; D011506:Proteins; D013879:Thioredoxins; D010088:Oxidoreductases; D013880:Thioredoxin-Disulfide Reductase; D019704:Protein Disulfide-Isomerases; D003545:Cysteine