6IMX
Crystal structure of V30M mutated transthyretin in complex with 18-Crown-6
Summary for 6IMX
| Entry DOI | 10.2210/pdb6imx/pdb |
| Descriptor | Transthyretin, 1,4,7,10,13,16-HEXAOXACYCLOOCTADECANE (3 entities in total) |
| Functional Keywords | transthyretin, amyloid, t4-binding protein, transport protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 35213.79 |
| Authors | Yokoyama, T.,Kosaka, Y.,Matsumoto, K.,Kitakami, R.,Nabeshima, Y.,Mizuguchi, M. (deposition date: 2018-10-24, release date: 2019-03-13, Last modification date: 2024-03-27) |
| Primary citation | 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 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.602 Å) |
Structure validation
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