4I85

Crystal structure of transthyretin in complex with CHF5074 at neutral pH

4I85 の概要

• エントリーDOI: 10.2210/pdb4i85/pdb
• 関連するPDBエントリー: 1DVT 1F41 1ROX 2G3X 3D2T 4I87 4I89
• 分子名称: Transthyretin, 1-(3',4'-dichloro-2-fluorobiphenyl-4-yl)cyclopropanecarboxylic acid (3 entities in total)
• 機能のキーワード: amyloidosis, fibrillogenesis, amyloid fibrils, t3 or t4 hormone binding, plasma, transport protein-inhibitor complex, transport protein/inhibitor
• 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: 28205.04

構造登録者

Zanotti, G.,Cendron, L.,Folli, C.,Florio, P.,Imbimbo, B.P.,Berni, R. (登録日: 2012-12-03, 公開日: 2013-06-19, 最終更新日: 2023-09-20)

主引用文献

Zanotti, G.,Cendron, L.,Folli, C.,Florio, P.,Imbimbo, B.P.,Berni, R.
Structural evidence for native state stabilization of a conformationally labile amyloidogenic transthyretin variant by fibrillogenesis inhibitors.
Febs Lett., 587:2325-2331, 2013

PubMed Abstract: Several classes of chemicals are able to bind to the thyroxine binding sites of transthyretin (TTR), stabilizing its native state and inhibiting in vitro the amyloidogenic process. The amyloidogenic I84S TTR variant undergoes a large conformational change at moderately acidic pH. Structural evidence has been obtained by X-ray analysis for the native state stabilization of I84S TTR by two chemically distinct fibrillogenesis inhibitors. In fact, they fully prevent the acidic pH-induced protein conformational change as a result of a long-range stabilizing effect. This study provides further support to the therapeutic strategy based on the use of TTR stabilizers as anti-amyloidogenic drugs.

PubMed: 23792159
DOI: 10.1016/j.febslet.2013.06.016

実験手法

X-RAY DIFFRACTION (1.67 Å)