{"reference": "J Am Chem Soc. 2005 Apr 20;127(15):5540-51", "alternative_name": "ATTR, Prealbumin, TBPA", "entry": "S-0068", "gene_names": "TTR, PALB", "remarks": "transthyretin with tethered inhibitor on one monomer.", "secondary_structure": "GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE#CCCCCCCCCCCEEEEEEETTTTEECCSCEEEEEEECTTSCEEEEEEEECCTTSEECCSCCTTTCCSEEEEEEECHHHHHHHTTCCCSEEEEEEEEEESTTSCCEEEEEEEEETTEEEEEEEEECCCC&GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE#CCCCCCCCCCCEEEEEEETTTTEECTTCEEEEEEECTTSCEEEEEEEECCTTSEECCSCCTTTCCSEEEEEEECHHHHHHHHTCCCSEEEEEEEEEECTTSCSEEEEEEEEETTEEEEEEEEECCCC", "chain_id": "A%%B", "inchi": "InChI=1S/C13H9Cl2NO5/c14-9-5-7(6-10(15)12(9)20-21-19)16-11-4-2-1-3-8(11)13(17)18/h1-6,16,19H,(H,17,18)%%InChI=1S/C13H9Cl2NO5/c14-9-5-7(6-10(15)12(9)20-21-19)16-11-4-2-1-3-8(11)13(17)18/h1-6,16,19H,(H,17,18)", "amyloid_non_amyloid": "Non-amyloid", "pmid": "15826192", "ligand_smiles": "c1ccc(c(c1)C(=O)O)Nc2cc(c(c(c2)Cl)OOO)Cl%%c1ccc(c(c1)C(=O)O)Nc2cc(c(c(c2)Cl)OOO)Cl", "keyword": "Transthyretin", "peptide_protein_sequence": "chain-ID A: GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE; chain-ID B: GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE", "uniprot_ac": "P02766", "protein_name": "Transthyretin", "r_value_free": "0.239", "mutation_s_field": "No", "ligand_mw": "330.12%%330.12", "pdb_id": "1U21", "inchi_key": "SNAMTVTZDPUVRA-UHFFFAOYSA-N%%SNAMTVTZDPUVRA-UHFFFAOYSA-N", "ec_number": "", "pdb_classification": "HORMONE/GROWTH FACTOR", "type": "Inhibitor complex", "author": "Wiseman, R.L., Johnson, S.M., Kelker, M.S., Foss, T., Wilson, I.A., Kelly, J.W.", "species": "Homo sapiens", "ligand_id": "P2C%%P2C", "method": "X-RAY DIFFRACTION", "ligand_name": "2-[(3,5-DICHLORO-4-TRIOXIDANYLPHENYL)AMINO]BENZOIC ACID%%2-[(3,5-DICHLORO-4-TRIOXIDANYLPHENYL)AMINO]BENZOIC ACID", "global_stoichiometry": "Homo 4-mer - A5", "resolution": "1.69", "ligand_formula": "C13 H9 Cl2 N O5%%C13 H9 Cl2 N O5", "length": "127", "ligstr": "P2C:A:C13 H9 Cl2 N O5:330.12:2-[(3,5-DICHLORO-4-TRIOXIDANYLPHENYL)AMINO]BENZOIC ACID:c1ccc(c(c1)C(=O)O)Nc2cc(c(c(c2)Cl)OOO)Cl:InChI=1S/C13H9Cl2NO5/c14-9-5-7(6-10(15)12(9)20-21-19)16-11-4-2-1-3-8(11)13(17)18/h1-6,16,19H,(H,17,18):SNAMTVTZDPUVRA-UHFFFAOYSA-N;P2C:B:C13 H9 Cl2 N O5:330.12:2-[(3,5-DICHLORO-4-TRIOXIDANYLPHENYL)AMINO]BENZOIC ACID:c1ccc(c(c1)C(=O)O)Nc2cc(c(c(c2)Cl)OOO)Cl:InChI=1S/C13H9Cl2NO5/c14-9-5-7(6-10(15)12(9)20-21-19)16-11-4-2-1-3-8(11)13(17)18/h1-6,16,19H,(H,17,18):SNAMTVTZDPUVRA-UHFFFAOYSA-N", "description": "Transthyretin (TTR) amyloidogenesis requires rate-limiting tetramer dissociation before misassembly of a partially denatured monomer ensues. Selective stabilization of the native TTR tetramer over the dissociative transition state by small molecule binding to both thyroxine binding sites raises the kinetic barrier of tetramer dissociation, preventing amyloidogenesis. Here, one fibril formation inhibitor tether to TTR by disulfide bond formation. Occupancy of only one of the two thyroxine binding sites is sufficient to inhibit tetramer dissociation in 6.0 M urea and amyloidogenesis under acidic conditions by imposing kinetic stabilization on the entire tetramer."}