Effect of curcumin on amyloidogenic property of molten globule-like intermediate state of 2,5-diketo-D-gluconate reductase A.
We identified a molten globule-like intermediate of 2,5-diketo-D-gluconate reductase A (DKGR) at pH 2.5, which has a prominent beta-sheet structure. The molten globule state of the protein shows amyloidogenic property >50 microm protein concentration. Interestingly, a 1:1 molar ratio of curcumin prevents amyloid formation as shown by the Thioflavin-T assay and atomic force microscopy. To the best of our knowledge, this is the first report on amyloid formation by an (alpha/beta)(8)-barrel protein. The results presented here indicate that the molten globule state has an important role in amyloid formation and potential application of curcumin in protein biotechnology as well as therapeutics against amyloid diseases.
Sarkar
Nandini
N
Department of Biotechnology, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India.
Singh
Abhay Narain
AN
Dubey
Vikash Kumar
VK
D000682:Amyloid / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D000686:Amyloidosis / Q000188:drug therapy / Q000378:metabolism; D052160:Benzothiazoles; D001681:Biological Assay; D002942:Circular Dichroism; D003474:Curcumin / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D018625:Microscopy, Atomic Force; D017510:Protein Folding / Q000187:drug effects; D017433:Protein Structure, Secondary; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D013401:Sugar Alcohol Dehydrogenases / Q000737:chemistry* / Q000378:metabolism*; D013844:Thiazoles / Q000378:metabolism; D013997:Time Factors
D000682:Amyloid; D052160:Benzothiazoles; D013844:Thiazoles; C009462:thioflavin T; D013401:Sugar Alcohol Dehydrogenases; C053163:2,5-diketo-D-gluconate 5-reductase; D003474:Curcumin