4PM1

Human transthyretin (TTR) complexed with 16-alpha-bromo-estradiol

4PM1 の概要

• エントリーDOI: 10.2210/pdb4pm1/pdb
• 関連するPDBエントリー: 3GS0 3GS4 4PME 4PMF
• 分子名称: Transthyretin, (14beta,16alpha,17alpha)-16-bromoestra-1,3,5(10)-triene-3,17-diol, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: human transthyretin hydrophobic ligand solubilization, thyroid hormone-binding 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: 28381.41

構造登録者

Stura, E.A.,Ciccone, L. (登録日: 2014-05-20, 公開日: 2014-10-08, 最終更新日: 2023-09-27)

主引用文献

Ciccone, L.,Tepshi, L.,Nencetti, S.,Stura, E.A.
Transthyretin complexes with curcumin and bromo-estradiol: evaluation of solubilizing multicomponent mixtures.
N Biotechnol, 32:54-64, 2014

PubMed Abstract: Crystallographic structure determination of protein-ligand complexes of transthyretin (TTR) has been hindered by the low affinity of many compounds that bind to the central cavity of the tetramer. Because crystallization trials are carried out at protein and ligand concentration that approach the millimolar range, low affinity is less of a problem than the poor solubility of many compounds that have been shown to inhibit amyloid fibril formation. To achieve complete occupancy in co-crystallization experiments, the minimal requirement is one ligand for each of the two sites within the TTR tetramer. Here we present a new strategy for the co-crystallization of TTR using high molecular weight polyethylene glycol instead of high ionic strength precipitants, with ligands solubilized in multicomponent mixtures of compounds. This strategy is applied to the crystallization of TTR complexes with curcumin and 16α-bromo-estradiol. Here we report the crystal structures with these compounds and with the ferulic acid that results from curcumin degradation.

PubMed: 25224922
DOI: 10.1016/j.nbt.2014.09.002

実験手法

X-RAY DIFFRACTION (1.23 Å)