{"method": "X-RAY DIFFRACTION", "mutation_s_field": "No", "ec_number": "", "description": "Tetramer dissociation is the rate-limiting step in TTR amyloidogenesis, targeted therapies have focused on small molecules that kinetically stabilize the tetramer, inhibiting TTR amyloid fibril formation. tafamidis meglumine (Fx-1006A), has recently completed Phase II/III trials for the treatment of Transthyretin Type Familial Amyloid Polyneuropathy (TTR-FAP) and demonstrated a slowing of disease progression in patients heterozygous for the V30M TTR mutation. Tafamidis binds selectively and with negative cooperativity to the two normally unoccupied thyroxine-binding sites of the tetramer, and kinetically stabilizes TTR. Patient-derived amyloidogenic variants of TTR, including kinetically and thermodynamically less stable mutants, are also stabilized by tafamidis binding.", "ligstr": "3MI:A:C14 H7 Cl2 N O3:308.12:2-(3,5-dichlorophenyl)-1,3-benzoxazole-6-carboxylic acid:c1cc2c(cc1C(=O)O)oc(n2)c3cc(cc(c3)Cl)Cl:InChI=1S/C14H7Cl2NO3/c15-9-3-8(4-10(16)6-9)13-17-11-2-1-7(14(18)19)5-12(11)20-13/h1-6H,(H,18,19):TXEIIPDJKFWEEC-UHFFFAOYSA-N;3MI:B:C14 H7 Cl2 N O3:308.12:2-(3,5-dichlorophenyl)-1,3-benzoxazole-6-carboxylic acid:c1cc2c(cc1C(=O)O)oc(n2)c3cc(cc(c3)Cl)Cl:InChI=1S/C14H7Cl2NO3/c15-9-3-8(4-10(16)6-9)13-17-11-2-1-7(14(18)19)5-12(11)20-13/h1-6H,(H,18,19):TXEIIPDJKFWEEC-UHFFFAOYSA-N", "pmid": "22645360", "remarks": "Structure of wild-type TTR in complex with tafamidis", "amyloid_non_amyloid": "Non-amyloid", "type": "Inhibitor complex", "inchi": "InChI=1S/C14H7Cl2NO3/c15-9-3-8(4-10(16)6-9)13-17-11-2-1-7(14(18)19)5-12(11)20-13/h1-6H,(H,18,19)%%InChI=1S/C14H7Cl2NO3/c15-9-3-8(4-10(16)6-9)13-17-11-2-1-7(14(18)19)5-12(11)20-13/h1-6H,(H,18,19)", "resolution": "1.3", "species": "Homo sapiens", "secondary_structure": "GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE#CCCCCCCCCCCEEEEEEETTTTEECCSCEEEEEEECTTSCEEEEEEEECCCCCEECCSCCTTTCCSEEEEEEECHHHHHHHTTCCCSEEEEEEEEEESTTSCCEEEEEEEEETTEEEEEEEEECCCC&GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE#CCCCCCCCCCCEEEEEEETTTTEECTTCEEEEEEECTTSCEEEEEEEECCTTSEECCSCCTTTCCSEEEEEEECHHHHHHHTTCCCSEEEEEEEEEECTTSCSEEEEEEEEETTEEEEEEEEECCCC", "chain_id": "A%%B", "gene_names": "TTR, PALB", "r_value_free": "0.192", "pdb_id": "3TCT", "reference": "Proc Natl Acad Sci U S A. 2012 Jun 12;109(24):9629-34.", "keyword": "Transthyretin", "protein_name": "Transthyretin", "ligand_formula": "C14 H7 Cl2 N O3%%C14 H7 Cl2 N O3", "peptide_protein_sequence": "chain-ID A: GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE; chain-ID B: GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE", "entry": "S-0305", "length": "127", "uniprot_ac": "P02766", "author": "Bulawa, C.E., Connelly, S., Devit, M., Wang, L., Weigel, C., Fleming, J.A., Packman, J., Powers, E.T., Wiseman, R.L., Foss, T.R., Wilson, I.A., Kelly, J.W., Labaudiniere, R.", "ligand_smiles": "c1cc2c(cc1C(=O)O)oc(n2)c3cc(cc(c3)Cl)Cl%%c1cc2c(cc1C(=O)O)oc(n2)c3cc(cc(c3)Cl)Cl", "ligand_mw": "308.12%%308.12", "alternative_name": "ATTR, Prealbumin, TBPA", "ligand_name": "2-(3,5-dichlorophenyl)-1,3-benzoxazole-6-carboxylic acid%%2-(3,5-dichlorophenyl)-1,3-benzoxazole-6-carboxylic acid", "pdb_classification": "HORMONE", "global_stoichiometry": "Homo 4-mer - A4", "inchi_key": "TXEIIPDJKFWEEC-UHFFFAOYSA-N%%TXEIIPDJKFWEEC-UHFFFAOYSA-N", "ligand_id": "3MI%%3MI"}