{"method": "X-RAY DIFFRACTION", "mutation_s_field": "No", "ec_number": "", "description": "They have designed ligands that are rapidly bound by native wild-type TTR in whole serum and even more avidly by amyloidogenic TTR variants. X-ray crystallographic analysis shows simultaneous occupation of both T4 binding sites in each tetrameric TTR molecule by the pair of ligand head groups. Ligand binding by native TTR was irreversible under physiological conditions, and it stabilized the tetrameric assembly and inhibited amyloidogenic aggregation more potently than other known ligands. These superstabilizers are orally bioavailable and exhibit low inhibitory activity against cyclooxygenase (COX).", "ligstr": "JZD:A:C37 H38 Cl4 N2 O6:748.52:2,2'-{undecane-1,11-diylbis[oxy(3,5-dichlorobenzene-4,1-diyl)imino]}dibenzoic acid:c1ccc(c(c1)C(=O)O)Nc2cc(c(c(c2)Cl)OCCCCCCCCCCCOc3c(cc(cc3Cl)Nc4ccccc4C(=O)O)Cl)Cl:InChI=1S/C37H38Cl4N2O6/c38-28-20-24(42-32-16-10-8-14-26(32)36(44)45)21-29(39)34(28)48-18-12-6-4-2-1-3-5-7-13-19-49-35-30(40)22-25(23-31(35)41)43-33-17-11-9-15-27(33)37(46)47/h8-11,14-17,20-23,42-43H,1-7,12-13,18-19H2,(H,44,45)(H,46,47):GZMGFINVSIBSLS-UHFFFAOYSA-N;JZD:B:C37 H38 Cl4 N2 O6:748.52:2,2'-{undecane-1,11-diylbis[oxy(3,5-dichlorobenzene-4,1-diyl)imino]}dibenzoic acid:c1ccc(c(c1)C(=O)O)Nc2cc(c(c(c2)Cl)OCCCCCCCCCCCOc3c(cc(cc3Cl)Nc4ccccc4C(=O)O)Cl)Cl:InChI=1S/C37H38Cl4N2O6/c38-28-20-24(42-32-16-10-8-14-26(32)36(44)45)21-29(39)34(28)48-18-12-6-4-2-1-3-5-7-13-19-49-35-30(40)22-25(23-31(35)41)43-33-17-11-9-15-27(33)37(46)47/h8-11,14-17,20-23,42-43H,1-7,12-13,18-19H2,(H,44,45)(H,46,47):GZMGFINVSIBSLS-UHFFFAOYSA-N", "pmid": "21059958", "remarks": "Human Transthyretin (TTR) complexed with a palindromic bivalent amyloid inhibitor (11 carbon linker).", "amyloid_non_amyloid": "Non-amyloid", "type": "Inhibitor complex", "inchi": "InChI=1S/C37H38Cl4N2O6/c38-28-20-24(42-32-16-10-8-14-26(32)36(44)45)21-29(39)34(28)48-18-12-6-4-2-1-3-5-7-13-19-49-35-30(40)22-25(23-31(35)41)43-33-17-11-9-15-27(33)37(46)47/h8-11,14-17,20-23,42-43H,1-7,12-13,18-19H2,(H,44,45)(H,46,47)%%InChI=1S/C37H38Cl4N2O6/c38-28-20-24(42-32-16-10-8-14-26(32)36(44)45)21-29(39)34(28)48-18-12-6-4-2-1-3-5-7-13-19-49-35-30(40)22-25(23-31(35)41)43-33-17-11-9-15-27(33)37(46)47/h8-11,14-17,20-23,42-43H,1-7,12-13,18-19H2,(H,44,45)(H,46,47)", "resolution": "1.9", "species": "Homo sapiens", "secondary_structure": "GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE#CCCCCCCCCCCEEEEEEETTTTEECTTCEEEEEEECTTSCEEEEEEEECCTTSEECCSCCTTTCCSEEEEEEECHHHHHHHTTCCCSEEEEEEEEEESTTSCCEEEEEEEEETTEEEEEEEEECCCC&GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE#CCCCCCCCCCCEEEEEEETTTTEECCSCEEEEEEECTTSCEEEEEEEECCTTSEECCSCCTTTCCSEEEEEEECHHHHHHHTTCCCSEEEEEEEEEECCCSSCEEEEEEEEETTEEEEEEEEECCCC", "chain_id": "A%%B", "gene_names": "TTR, PALB", "r_value_free": "0.22899999", "pdb_id": "3IPB", "reference": "Proc Natl Acad Sci U S A. 2010 Nov 23;107(47):20483-8.", "keyword": "Transthyretin", "protein_name": "Transthyretin", "ligand_formula": "C37 H38 Cl4 N2 O6%%C37 H38 Cl4 N2 O6", "peptide_protein_sequence": "chain-ID A: GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE; chain-ID B: GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE", "entry": "S-0258", "length": "127", "uniprot_ac": "P02766", "author": "Kolstoe, S.E., Mangione, P.P., Bellotti, V., Taylor, G.W., Tennent, G.A., Deroo, S., Morrison, A.J., Cobb, A.J., Coyne, A., McCammon, M.G., Warner, T.D., Mitchell, J., Gill, R., Smith, M.D., Ley, S.V., Robinson, C.V., Wood, S.P., Pepys, M.B.", "ligand_smiles": "c1ccc(c(c1)C(=O)O)Nc2cc(c(c(c2)Cl)OCCCCCCCCCCCOc3c(cc(cc3Cl)Nc4ccccc4C(=O)O)Cl)Cl%%c1ccc(c(c1)C(=O)O)Nc2cc(c(c(c2)Cl)OCCCCCCCCCCCOc3c(cc(cc3Cl)Nc4ccccc4C(=O)O)Cl)Cl", "ligand_mw": "748.52%%748.52", "alternative_name": "ATTR, Prealbumin, TBPA", "ligand_name": "2,2'-{undecane-1,11-diylbis[oxy(3,5-dichlorobenzene-4,1-diyl)imino]}dibenzoic acid%%2,2'-{undecane-1,11-diylbis[oxy(3,5-dichlorobenzene-4,1-diyl)imino]}dibenzoic acid", "pdb_classification": "HORMONE", "global_stoichiometry": "Homo 4-mer - A4 ", "inchi_key": "GZMGFINVSIBSLS-UHFFFAOYSA-N%%GZMGFINVSIBSLS-UHFFFAOYSA-N", "ligand_id": "JZD%%JZD"}