6TJN

Human transthyretin (TTR) complexed with (E)-3-(((4-hydroxybenzylidene)amino)oxy)propanoic acid

6TJN の概要

• エントリーDOI: 10.2210/pdb6tjn/pdb
• 分子名称: Transthyretin, 3-[(~{E})-(4-hydroxyphenyl)methylideneamino]oxypropanoic acid (3 entities in total)
• 機能のキーワード: transthyretin, ttr, inhibitor, complex, protein transport
• 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: 28087.22

構造登録者

Ciccone, L.,Shepard, W.,Nencetti, S.,Orlandini, E.,Rossello, A. (登録日: 2019-11-26, 公開日: 2020-12-16, 最終更新日: 2024-01-24)

主引用文献

Ciccone, L.,Nencetti, S.,Tonali, N.,Fruchart-Gaillard, C.,Shepard, W.,Nuti, E.,Camodeca, C.,Rossello, A.,Orlandini, E.
Monoaryl derivatives as transthyretin fibril formation inhibitors: Design, synthesis, biological evaluation and structural analysis.
Bioorg.Med.Chem., 28:115673-115673, 2020

PubMed Abstract: Transthyretin (TTR) is a ß-sheet-rich homotetrameric protein that transports thyroxine (T4) and retinol both in plasma and in cerebrospinal fluid. TTR also interacts with amyloid-β, playing a protective role in Alzheimer's disease. Dissociation of the native transthyretin (TTR) tetramer is widely accepted as the critical step in TTR amyloids fibrillogenesis, and is responsible for extracellular deposition of amyloid fibrils. Small molecules, able to bind in T4 binding sites and stabilize the TTR tetramer, are interesting tools to treat and prevent systemic ATTR amyloidosis. We report here the synthesis, in vitro evaluation and three-dimensional crystallographic analyses of new monoaryl-derivatives in complex with TTR. Of the derivatives reported here, the best inhibitor of TTR fibrillogenesis, 1d, exhibits an activity similar to diflunisal.

PubMed: 32828431
DOI: 10.1016/j.bmc.2020.115673

実験手法

X-RAY DIFFRACTION (1.702 Å)