{"method": "X-RAY DIFFRACTION", "mutation_s_field": "No", "ec_number": "", "description": "Monovalent small molecules that bind to one or both of the unoccupied thyroid hormone binding sites at the TTR quaternary structure interface stabilize the native state. Bivalent amyloid inhibitors that bind to both binding sites simultaneously are reported here. The candidate bivalent inhibitors are generally unable to bind to the native TTR tetramer and typically do not engage in monovalent binding owing to a strong inhibitor orientation preference. However, the TTR quaternary structure can assemble around several of the bivalent inhibitors if the inhibitor intercepts the protein before assembly occurs. Some of the wild-type TTR.bivalent inhibitor complexes prepared in this fashion retain a tetrameric structure when subjected to substantial denaturation stresses (8 M urea, 120 h).", "ligstr": "44C:A:C30 H27 N O6:497.54:4'-(4-{4-[(2-CARBOXYPHENYL)AMINO]PHENOXY}BUTOXY)-1,1'-BIPHENYL-4-CARBOXYLIC ACID:c1ccc(c(c1)C(=O)O)Nc2ccc(cc2)OCCCCOc3ccc(cc3)c4ccc(cc4)C(=O)O:InChI=1S/C30H27NO6/c32-29(33)23-9-7-21(8-10-23)22-11-15-25(16-12-22)36-19-3-4-20-37-26-17-13-24(14-18-26)31-28-6-2-1-5-27(28)30(34)35/h1-2,5-18,31H,3-4,19-20H2,(H,32,33)(H,34,35):PBSDQYSNDJNJGR-UHFFFAOYSA-N", "pmid": "14583036", "remarks": "Human transthyretin (TTR) complexed with bivalant amyloid inhibitor (4 carbon linker)", "amyloid_non_amyloid": "Non-amyloid", "type": "Inhibitor complex", "inchi": "InChI=1S/C30H27NO6/c32-29(33)23-9-7-21(8-10-23)22-11-15-25(16-12-22)36-19-3-4-20-37-26-17-13-24(14-18-26)31-28-6-2-1-5-27(28)30(34)35/h1-2,5-18,31H,3-4,19-20H2,(H,32,33)(H,34,35)", "resolution": "1.46", "species": "Homo sapiens", "secondary_structure": "GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE#CCCCCCCCCCCEEEEEEETTTTEECCSCEEEEEEECTTSCEEEEEEEECCTTSEECCSCCTTTCCSEEEEEEECHHHHHHHTTCCCSEEEEEEEEEESTTSCCEEEEEEEEETTEEEEEEEEECCCC&GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE#CCCCCCCCCCCEEEEEEETTTTEECTTCEEEEEEECTTSCEEEEEEEECCTTSEECCSCCTTTCCSEEEEEEECHHHHHHHTTCCCSBSCEEEEEEECSSSCSCEEEEEEEETTEEEEEEEECCCCC", "chain_id": "A", "gene_names": "TTR, PALB", "r_value_free": "0.22399999", "pdb_id": "2FBR", "reference": "J Am Chem Soc. 2003 Nov 5;125(44):13404-14", "keyword": "Transthyretin", "protein_name": "Transthyretin", "ligand_formula": "C30 H27 N O6", "peptide_protein_sequence": "chain-ID A: GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE; chain-ID B: GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE", "entry": "S-0099", "length": "127", "uniprot_ac": "P02766", "author": "Green, N.S., Palaninathan, S.K., Sacchettini, J.C., Kelly, J.W.", "ligand_smiles": "c1ccc(c(c1)C(=O)O)Nc2ccc(cc2)OCCCCOc3ccc(cc3)c4ccc(cc4)C(=O)O", "ligand_mw": "497.54", "alternative_name": "ATTR, Prealbumin, TBPA", "ligand_name": "4'-(4-{4-[(2-CARBOXYPHENYL)AMINO]PHENOXY}BUTOXY)-1,1'-BIPHENYL-4-CARBOXYLIC ACID", "pdb_classification": "HORMONE/GROWTH FACTOR", "global_stoichiometry": "Homo 4-mer - A4 ", "inchi_key": "PBSDQYSNDJNJGR-UHFFFAOYSA-N", "ligand_id": "44C"}