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PDI and glutathione‐mediated reduction of the glutathionylated variant of human lysozyme
Author(s) -
Hayano Toshiya,
Inaka Koji,
Otsu Mieko,
Taniyama Yoshio,
Miki Kunio,
Matsushima Masaaki,
Kikuchi Masakazu
Publication year - 1993
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(93)80993-5
Subject(s) - protein disulfide isomerase , lysozyme , glutathione , chemistry , thioredoxin , protein folding , endoplasmic reticulum , folding (dsp implementation) , biochemistry , oxidative folding , protein structure , glutathione disulfide , native state , enzyme , electrical engineering , engineering
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.