{"remarks": "CRYSTAL STRUCTURE OF HUMAN TRANSTHYRETIN IN COMPLEX WITH DICLOFENAC", "ligand_id": "DIF", "secondary_structure": "GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEQFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTN#CCCCCCCCCCCEEEEEEETTTTEECTTCEEEEEEECTTSCEEEEEEEECCTTSEECCSCCTTTCCSEEEEEEECHHHHHHHTTCCCSEEEEEEEEEESTTSCCEEEEEEEEETTEEEEEEEEEC&GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEQFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTN#CCCCCCCCCCCEEEEEEETTTTEECTTCEEEEEEECTTSCEEEEEEEECCTTSEECCSCCTTTCCSEEEEEEECHHHHHHHTTCCCSEEEEEEEEEECCCSSCCEEEEEEEETTEEEEEEEECC", "mutation_s_field": "No", "keyword": "TRANSTHYRETIN", "ligstr": "DIF:B:C14 H11 Cl2 N O2:296.15:2-[2,6-DICHLOROPHENYL)AMINO]BENZENEACETIC ACID:c1ccc(c(c1)CC(=O)O)Nc2c(cccc2Cl)Cl:InChI=1S/C14H11Cl2NO2/c15-10-5-3-6-11(16)14(10)17-12-7-2-1-4-9(12)8-13(18)19/h1-7,17H,8H2,(H,18,19):DCOPUUMXTXDBNB-UHFFFAOYSA-N", "alternative_name": "ATTR, Prealbumin, TBPA", "species": "Homo sapiens", "r_value_free": "0.215", "pdb_id": "1DVX", "pmid": "10742177", "peptide_protein_sequence": "chain-ID A: GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEQFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTN; chain-ID B: GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEQFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTN", "resolution": "2.0", "ec_number": "", "uniprot_ac": "P02766", "protein_name": "Transthyretin", "global_stoichiometry": "Homo 4-mer - A4 ", "ligand_smiles": "c1ccc(c(c1)CC(=O)O)Nc2c(cccc2Cl)Cl", "author": "Klabunde, T., Petrassi, H.M., Oza, V.B., Raman, P., Kelly, J.W., Sacchettini, J.C.", "description": "DIC bind TTR and inhibit TTR amyloid formation is elucidated. Metabolic stability, significant oral absorption, and low toxicity have already been proven for the drug in numerous clinical trials. Due to the superior gastrointestinal tolerability of DIC it is more likely to have clinical utility as a chemotherapy treatment of human TTR-associated amyloid diseases. TTR\u00e2\u20ac\u201cDIC complex showed that the inhibitor has good steric complementarity with the T4 binding site. The active, propeller-like conformation of the inhibitor bound to TTR was close to the lowest energy conformation of the compound. Due to the two-fold symmetry of the binding cavity, DIC was found in two binding modes (DIC1 and DIC2) that are related by a 180\u00c2\u00b0 rotation along the hormone binding channel. DIC forms interactions with residues Lys 15, Leu 17, Ala 108, Leu 110, Ser 117, Thr 119, and Val 121 of two adjacent TTR subunits, thus mediating several intersubunit interactions. SAR demonstrated that the hydrogen bond between the carboxylate group of the inhibitor and Thr 119 contributes to diclofenac's affinity for TTR and its potency as a fibril formation inhibitor.", "ligand_mw": "296.15", "entry": "S-0021", "ligand_name": "2-[2,6-DICHLOROPHENYL)AMINO]BENZENEACETIC ACID", "pdb_classification": "HORMONE/GROWTH FACTOR", "amyloid_non_amyloid": "Non-amyloid", "chain_id": "B", "inchi_key": "DCOPUUMXTXDBNB-UHFFFAOYSA-N", "gene_names": "TTR, PALB", "method": "X-RAY DIFFRACTION", "length": "124", "inchi": "InChI=1S/C14H11Cl2NO2/c15-10-5-3-6-11(16)14(10)17-12-7-2-1-4-9(12)8-13(18)19/h1-7,17H,8H2,(H,18,19)", "type": "Inhibitor complex", "reference": "Nat Struct Biol. 2000 Apr;7(4):312-21", "ligand_formula": "C14 H11 Cl2 N O2"}