Impact of an easily reducible disulfide bond on the oxidative folding rate of multi-disulfide-containing proteins

:  The burial of native disulfide bonds, formed within stable structure in the regeneration of multi‐disulfide‐containing proteins from their fully reduced states, is a key step in the folding process, as the burial greatly accelerates the oxidative folding rate of the protein by sequestering the na...

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Bibliographic Details
Published in:The journal of peptide research 2005-01, Vol.65 (1), p.47-54
Main Authors: Leung, H.J., Xu, G., Narayan, M., Scheraga, H.A.
Format: Article
Language:English
Subjects:
Animals
Cattle
Chromatography, High Pressure Liquid
Circular Dichroism
disulfide bond burial
Disulfides - chemistry
Disulfides - metabolism
easily reducible disulfide
Enzyme Stability
Kinetics
Models, Molecular
Mutation - genetics
native structure
Oxidation-Reduction
oxidative folding
Protein Folding
Protein Structure, Tertiary
redox reagent
reductive unfolding
Ribonuclease, Pancreatic - chemistry
Ribonuclease, Pancreatic - genetics
Ribonuclease, Pancreatic - metabolism
Tyrosine - genetics
Tyrosine - metabolism
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Summary::  The burial of native disulfide bonds, formed within stable structure in the regeneration of multi‐disulfide‐containing proteins from their fully reduced states, is a key step in the folding process, as the burial greatly accelerates the oxidative folding rate of the protein by sequestering the native disulfide bonds from thiol‐disulfide exchange reactions. Nevertheless, several proteins retain solvent‐exposed disulfide bonds in their native structures. Here, we have examined the impact of an easily reducible native disulfide bond on the oxidative folding rate of a protein. Our studies reveal that the susceptibility of the (40–95) disulfide bond of Y92G bovine pancreatic ribonuclease A (RNase A) to reduction results in a reduced rate of oxidative regeneration, compared with wild‐type RNase A. In the native state of RNase A, Tyr 92 lies atop its (40–95) disulfide bond, effectively shielding this bond from the reducing agent, thereby promoting protein oxidative regeneration. Our work sheds light on the unique contribution of a local structural element in promoting the oxidative folding of a multi‐disulfide‐containing protein.
ISSN:1397-002X
1399-3011
DOI:10.1111/j.1399-3011.2004.00189.x