5AYT

Crystal structure of transthyretin in complex with L6

5AYT の概要

• エントリーDOI: 10.2210/pdb5ayt/pdb
• 分子名称: Transthyretin, 2-oxidanyl-6-(phenylcarbonyl)benzo[de]isoquinoline-1,3-dione (3 entities in total)
• 機能のキーワード: amyloidogenic protein, inhibitor, stabilizer, drug discovery, transport protein-inhibitor complex, transport protein/inhibitor
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 35255.63

構造登録者

Yokoyama, T.,Mizuguchi, M.,Kai, H. (登録日: 2015-09-03, 公開日: 2016-01-20, 最終更新日: 2024-03-20)

主引用文献

Yokoyama, T.,Takaki, S.,Chosa, K.,Sato, T.,Suico, M.A.,Teranishi, Y.,Shuto, T.,Mizuguchi, M.,Kai, H.
Structural stabilization of transthyretin by a new compound, 6-benzoyl-2-hydroxy-1H-benzo[de]isoquinoline-1,3(2H)-dione
J. Pharmacol. Sci., 129:240-243, 2015

PubMed Abstract: Familial amyloid polyneuropathy (FAP) is a genetic, adult-onset, neurodegenerative disorder caused by amyloid formation of transthyretin (TTR), a thyroxine-binding protein. Mutation in TTR causes a propensity of TTR tetramer to dissociate to monomer, which is the first step to amyloidosis. Thus, a drug that can stabilize the tetramer structure will have therapeutic benefit. Here, by virtual screening and biochemical assays, we identified small molecule 6-benzoyl-2-hydroxy-1H-benzo[de]isoquinoline-1,3(2H)-dione (L6) that can prevent the dissociation of TTR to monomer. X-ray crystallography reveals that L6 binds to the T4 binding pocket of TTR. These findings show that L6 is a candidate TTR stabilizer.

PubMed: 26639444
DOI: 10.1016/j.jphs.2015.09.006

実験手法

X-RAY DIFFRACTION (1.4 Å)