Acceleration of oxidative protein folding by curcumin through novel non-redox chemistry.
Curcumin, the major constituent of turmeric is a known antioxidant. We have examined the oxidative folding of the model four-disulfide-bond-containing protein bovine pancreatic ribonuclease A (RNase A) in its presence; results indicate that RNase A regeneration rate increases in a curcumin-dependent manner. Examination of the native tendency of the fully-reduced polypeptide and the stability of key folding intermediates suggests that the increased oxidative folding rate can be attributed to native-like elements induced within the fully-reduced polypeptide and the stabilization of native-like species by this non-redox-active natural product. Our results provide a template for the design of curcuminoid-based synthetic small-molecule fold catalysts that accelerate the folding of ER-processed proteins; this assumes significance given that nitrosative stress and dysfunction of the ER-resident oxidoreductase protein disulfide isomerise due to S-nitrosylation are factors associated with the pathogenesis of Alzheimer's and Parkinson's diseases.
Gomez
Gabriel
G
Department of Biological Sciences, University of Texas at El Paso, El Paso, TX 79968, USA.
Mansouraty
Gabriel
G
Gardea
Jessica
J
Narayan
Mahesh
M
D003474:Curcumin / Q000737:chemistry*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry*; D017510:Protein Folding; D012259:Ribonuclease, Pancreatic / Q000737:chemistry* / Q000648:ultrastructure*; D013997:Time Factors
D012259:Ribonuclease, Pancreatic; D003474:Curcumin; D010100:Oxygen