title: (-)-epigallocatechin-3-gallate inhibits fibrillogenesis of chicken cystatin.
abstract: Previous studies have reported that (-)-epigallocatechin-3-gallate (EGCG), the most abundant flavonoid in green tea, can bind to unfolded native polypeptides and prevent conversion to amyloid fibrils. To elucidate whether this antifibril activity is specific to disease-related target proteins or is more generic, we investigated the ability of EGCG to inhibit amyloid fibril formation of amyloidogenic mutant chicken cystatin I66Q, a generic amyloid-forming model protein that undergoes fibril formation through a domain swapping mechanism. We demonstrated that EGCG was a potent inhibitor of amyloidogenic cystatin I66Q amyloid fibril formation in vitro. Computational analysis suggested that EGCG prevented amyloidogenic cystatin fibril formation by stabilizing the molecule in its native-like state as opposed to redirecting aggregation toward disordered and amorphous aggregates. Therefore, although EGCG appears to be a generic inhibitor of amyloid-fibril formation, the mechanism by which it achieves such inhibition may be specific to the target fibril-forming polypeptide.
authors.affiliation: Province Key Laboratory of Animal Resource and Epidemic Disease Prevention, School of Life Science, Liaoning University , Shenyang 110036, China.
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.forename: Jianwei
authors.initials: J
authors.lastname: He
authors.forename: Alan K
authors.initials: AK
authors.lastname: Chang
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Linan
authors.initials: L
authors.lastname: Xu
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Chong
authors.forename: Xian
authors.initials: X
authors.lastname: Lu
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Sun
authors.forename: Xichun
authors.initials: X
authors.lastname: Xia
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.forename: Youtao
authors.initials: Y
authors.lastname: Song
authors.forename: Akio
authors.initials: A
authors.lastname: Kato
authors.forename: Gary W
authors.initials: GW
authors.lastname: Jones
mesh_terms: D000682:Amyloid / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002645:Chickens; D015891:Cystatins / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D062105:Molecular Docking Simulation; D009154:Mutation; D011485:Protein Binding; D017433:Protein Structure, Secondary / Q000187:drug effects
chemical_list: D000682:Amyloid; D015891:Cystatins; C100158:cystatin, egg-white; D002392:Catechin; C045651:epigallocatechin gallate
keywords: (−)-epigallocatechin-3-gallate; amyloid; cystatin; molecular docking; molecular dynamics simulation