5AYT
Crystal structure of transthyretin in complex with L6
Summary for 5AYT
| Entry DOI | 10.2210/pdb5ayt/pdb |
| Descriptor | Transthyretin, 2-oxidanyl-6-(phenylcarbonyl)benzo[de]isoquinoline-1,3-dione (3 entities in total) |
| Functional Keywords | amyloidogenic protein, inhibitor, stabilizer, drug discovery, transport protein-inhibitor complex, transport protein/inhibitor |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 35255.63 |
| Authors | Yokoyama, T.,Mizuguchi, M.,Kai, H. (deposition date: 2015-09-03, release date: 2016-01-20, Last modification date: 2024-03-20) |
| Primary citation | Yokoyama, T.,Takaki, S.,Chosa, K.,Sato, T.,Suico, M.A.,Teranishi, Y.,Shuto, T.,Mizuguchi, M.,Kai, H. Structural stabilization of transthyretin by a new compound, 6-benzoyl-2-hydroxy-1H-benzo[de]isoquinoline-1,3(2H)-dione J. Pharmacol. Sci., 129:240-243, 2015 Cited by PubMed Abstract: Familial amyloid polyneuropathy (FAP) is a genetic, adult-onset, neurodegenerative disorder caused by amyloid formation of transthyretin (TTR), a thyroxine-binding protein. Mutation in TTR causes a propensity of TTR tetramer to dissociate to monomer, which is the first step to amyloidosis. Thus, a drug that can stabilize the tetramer structure will have therapeutic benefit. Here, by virtual screening and biochemical assays, we identified small molecule 6-benzoyl-2-hydroxy-1H-benzo[de]isoquinoline-1,3(2H)-dione (L6) that can prevent the dissociation of TTR to monomer. X-ray crystallography reveals that L6 binds to the T4 binding pocket of TTR. These findings show that L6 is a candidate TTR stabilizer. PubMed: 26639444DOI: 10.1016/j.jphs.2015.09.006 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.4 Å) |
Structure validation
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