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6IMX

Crystal structure of V30M mutated transthyretin in complex with 18-Crown-6

6IMX の概要
エントリーDOI10.2210/pdb6imx/pdb
分子名称Transthyretin, 1,4,7,10,13,16-HEXAOXACYCLOOCTADECANE (3 entities in total)
機能のキーワードtransthyretin, amyloid, t4-binding protein, transport protein
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35213.79
構造登録者
Yokoyama, T.,Kosaka, Y.,Matsumoto, K.,Kitakami, R.,Nabeshima, Y.,Mizuguchi, M. (登録日: 2018-10-24, 公開日: 2019-03-13, 最終更新日: 2024-03-27)
主引用文献Yokoyama, T.,Mizuguchi, M.
Crown Ethers as Transthyretin Amyloidogenesis Inhibitors.
J. Med. Chem., 62:2076-2082, 2019
Cited by
PubMed Abstract: Transthyretin (TTR) is a tetrameric protein found in human serum and associated with amyloid diseases. Because the tetramer dissociation and misfolding of the monomer precede amyloid fibril formation, development of a small molecule that binds to TTR and stabilizes the TTR tetramer is an efficient strategy for the treatment of amyloidosis. Here, we report our discovery of the anti-TTR amyloidogenesis activities of crown ethers. X-ray crystallographic analysis, binding assay, and chemical cross-linking assay showed that 4'-carboxybenzo-18C6 (4) stabilized the TTR tetramer by binding to the allosteric sites on the molecular surface of the TTR tetramer. In addition, 4 synergistically increased the stabilization activity of diflunisal, one of the most potent TTR amyloidogenesis inhibitors. These experimental evidences establish that 4 is a valuable template compound as an allosteric inhibitor of TTR amyloidogenesis.
PubMed: 30688456
DOI: 10.1021/acs.jmedchem.8b01700
主引用文献が同じPDBエントリー
実験手法
X-RAY DIFFRACTION (1.602 Å)
構造検証レポート
Validation report summary of 6imx
検証レポート(詳細版)ダウンロードをダウンロード

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件を2025-07-09に公開中

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