3NG5

Crystal Structure of V30M transthyretin complexed with (-)-epigallocatechin gallate (EGCG)

3NG5 の概要

• エントリーDOI: 10.2210/pdb3ng5/pdb
• 分子名称: Transthyretin, (2R,3R)-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-chromen-3-yl 3,4,5-trihydroxybenzoate, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: retinol-binding, secreted, thyroid hormone, transport, vitamin a, transport protein, thyroxine
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P02766
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 29086.06

構造登録者

Miyata, M.,Nakamura, T.,Ikemizu, S.,Chirifu, M.,Yamagata, Y.,Kai, H. (登録日: 2010-06-11, 公開日: 2010-07-07, 最終更新日: 2023-11-01)

主引用文献

Miyata, M.,Sato, T.,Kugimiya, M.,Sho, M.,Nakamura, T.,Ikemizu, S.,Chirifu, M.,Mizuguchi, M.,Nabeshima, Y.,Suwa, Y.,Morioka, H.,Arimori, T.,Suico, M.A.,Shuto, T.,Sako, Y.,Momohara, M.,Koga, T.,Morino-Koga, S.,Yamagata, Y.,Kai, H.
Crystal structure of green tea polyphenol(-)-epigallocatechin gallate (EGCG)-transthyretin complex reveals novel binding site distinct from thyroxine binding site
Biochemistry, 2010

PubMed Abstract: Amyloid fibril formation is associated with protein misfolding disorders, including neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's diseases. Familial amyloid polyneuropathy (FAP) is a hereditary disease caused by a point mutation of the human plasma protein, transthyretin (TTR), which binds and transports thyroxine (T(4)). TTR variants contribute to the pathogenesis of amyloidosis by forming amyloid fibrils in the extracellular environment. A recent report showed that epigallocatechin 3-gallate (EGCG), the major polyphenol component of green tea, binds to TTR and suppresses TTR amyloid fibril formation. However, structural analysis of EGCG binding to TTR has not yet been conducted. Here we first investigated the crystal structure of the EGCG-V30M TTR complex and found novel binding sites distinct from the thyroxine binding site, suggesting that EGCG has a mode of action different from those of previous chemical compounds that were shown to bind and stabilize the TTR tetramer structure. Furthermore, EGCG induced the oligomerization and monomer suppression in the cellular system of clinically reported TTR variants. Taken together, these findings suggest the possibility that EGCG may be a candidate compound for FAP therapy.

PubMed: 20565072
DOI: 10.1021/bi1004409

実験手法

X-RAY DIFFRACTION (1.7 Å)