4PWF

Crystal structure of V30M mutant human transthyretin complexed with ferulic acid phenethyl ester

4PWF の概要

• エントリーDOI: 10.2210/pdb4pwf/pdb
• 関連するPDBエントリー: 4PWE 4PWG 4PWH 4PWI 4PWJ 4PWK
• 分子名称: Transthyretin, 2-phenylethyl (2E)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enoate (3 entities in total)
• 機能のキーワード: tranporter, thyroxine binding, transport protein
• 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: 35281.83

構造登録者

Yokoyama, T.,Kosaka, Y.,Mizuguchi, M. (登録日: 2014-03-20, 公開日: 2014-11-26, 最終更新日: 2023-11-08)

主引用文献

Yokoyama, T.,Kosaka, Y.,Mizuguchi, M.
Inhibitory Activities of Propolis and Its Promising Component, Caffeic Acid Phenethyl Ester, against Amyloidogenesis of Human Transthyretin
J.Med.Chem., 57:8928-8935, 2014

PubMed Abstract: Transthyretin (TTR) is a homotetrameric serum protein associated with amyloidoses such as familial amyloid polyneuropathy and senile systemic amyloidosis. The amyloid fibril formation of TTR can be inhibited through stabilization of the TTR tetramer by the binding of small molecules. In this study, we examined the inhibitory potency of caffeic acid phenethyl ester (CAPE) and its derivatives. Thioflavin T assay showed that CAPE suppressed the amyloid fibril formation of TTR. Comparative analysis of the inhibitory potencies revealed that phenethyl ferulate was the most potent among the CAPE derivatives. The binding of phenethyl ferulate and the selected compounds to TTR were confirmed by the 8-anilino-1-naphthalenesulfonic acid displacement and X-ray crystallography. It was also demonstrated that Bio 30, which is a CAPE-rich commercially available New Zealand propolis, inhibited TTR amyloidogenesis and stabilized the TTR tetramer. These results suggested that a propolis may be efficient for preventing TTR amyloidosis.

PubMed: 25314129
DOI: 10.1021/jm500997m

実験手法

X-RAY DIFFRACTION (1.6 Å)