5EZP

Human transthyretin (TTR) complexed with 4-hydroxy-chalcone

5EZP の概要

• エントリーDOI: 10.2210/pdb5ezp/pdb
• 関連するPDBエントリー: 4I89 4PM1 4PMF 4WNS 5AKS
• 分子名称: Transthyretin, 4-hydroxy-chalcone, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: human transthyretin (ttr), chalcone, inhibitor complex, new crystal polymorph, 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: 8
• 化学式量合計: 108094.82

構造登録者

Polsinelli, I.,Nencetti, S.,Shepard, W.E.,Orlandini, E.,Stura, E.A. (登録日: 2015-11-26, 公開日: 2016-01-27, 最終更新日: 2024-01-10)

主引用文献

Polsinelli, I.,Nencetti, S.,Shepard, W.,Ciccone, L.,Orlandini, E.,Stura, E.A.
A new crystal form of human transthyretin obtained with a curcumin derived ligand.
J.Struct.Biol., 194:8-17, 2016

PubMed Abstract: Transthyretin (TTR), a 54kDa homotetrameric protein that transports thyroxine (T4), has been associated with clinical cases of TTR amyloidosis for its tendency to aggregate to form fibrils. Many ligands with a potential to inhibit fibril formation have been studied by X-ray crystallography in complex with TTR. Unfortunately, the ligand is often found in ambiguous electron density that is difficult to interpret. The ligand validation statistics suggest over-interpretation, even for the most active compounds like diflunisal. The primary technical reason is its position on a crystallographic 2-fold axis in the most common crystal form. Further investigations with the use of polyethylene glycol (PEG) to crystallize TTR complexes have resulted in a new trigonal polymorph with two tetramers in the asymmetric unit. The ligand used to obtain this new polymorph, 4-hydroxychalcone, is related to curcumin. Here we evaluate this crystal form to understand the contribution it may bring to the study of TTR ligands complexes, which are often asymmetric.

PubMed: 26796656
DOI: 10.1016/j.jsb.2016.01.007

実験手法

X-RAY DIFFRACTION (2.5 Å)