6IMX
Crystal structure of V30M mutated transthyretin in complex with 18-Crown-6
6IMX の概要
エントリーDOI | 10.2210/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: 30688456DOI: 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) |
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