{"method": "X-RAY DIFFRACTION", "mutation_s_field": "No", "ec_number": "", "description": "Ex vivo and in vitro studies have revealed the remarkable amyloid inhibitory potency and specificity of iododiflunisal in relation to transthyretin. the crystal structure of transthyretin complexed with this diflunisal derivative is reported, which enables a detailed analysis of the protein-ligand interactions. Iododiflunisal binds very deep in the hormone-binding channel. The iodine substituent is tightly anchored into a pocket of the binding site and the fluorine atoms provide extra hydrophobic contacts with the protein. The carboxylate substituent is involved in an electrostatic interaction with the N(zeta) of a lysine residue. Moreover, ligand-induced conformational alterations in the side chain of some residues result in the formation of new intersubunit hydrogen bonds. All these new interactions, induced by iododiflunisal, increase the stability of the tetramer impairing the formation of amyloid fibrils.", "ligstr": "FHI:A:C13 H7 F2 I O3:376.09:2',4'-DIFLUORO-4-HYDROXY-5-IODO-1,1'-BIPHENYL-3-CARBOXYLIC ACID:c1cc(c(cc1F)F)c2cc(c(c(c2)I)O)C(=O)O:InChI=1S/C13H7F2IO3/c14-7-1-2-8(10(15)5-7)6-3-9(13(18)19)12(17)11(16)4-6/h1-5,17H,(H,18,19):SSYOLLIRAAWGDJ-UHFFFAOYSA-N;FHI:B:C13 H7 F2 I O3:376.09:2',4'-DIFLUORO-4-HYDROXY-5-IODO-1,1'-BIPHENYL-3-CARBOXYLIC ACID:c1cc(c(cc1F)F)c2cc(c(c(c2)I)O)C(=O)O:InChI=1S/C13H7F2IO3/c14-7-1-2-8(10(15)5-7)6-3-9(13(18)19)12(17)11(16)4-6/h1-5,17H,(H,18,19):SSYOLLIRAAWGDJ-UHFFFAOYSA-N", "pmid": "15689188", "remarks": "Human transthyretin in complex with iododiflunisal", "amyloid_non_amyloid": "Non-amyloid", "type": "Inhibitor complex", "inchi": "InChI=1S/C13H7F2IO3/c14-7-1-2-8(10(15)5-7)6-3-9(13(18)19)12(17)11(16)4-6/h1-5,17H,(H,18,19)%%InChI=1S/C13H7F2IO3/c14-7-1-2-8(10(15)5-7)6-3-9(13(18)19)12(17)11(16)4-6/h1-5,17H,(H,18,19)", "resolution": "1.7", "species": "Homo sapiens", "secondary_structure": "GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE#CCCCCCCCCCCEEEEEEETTTTEECTTCEEEEEEECTTSCEEEEEEEECCTTSEECCSCCTTTCCSEEEEEEECHHHHHHHHTCCCSEEEEEEEEEECSSSCSCEEEEEEEETTEEEEEEEECCCCC&GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE#CCCCCCCCCCCEEEEEEETTTTEECCSCEEEEEEECTTSCEEEEEEEECCTTSEECCSCCTTTCCSEEEEEEECHHHHHHHTTCCCSEEEEEEEEEESTTSCCEEEEEEEEETTEEEEEEEEECCCC", "chain_id": "A%%B", "gene_names": "TTR, PALB", "r_value_free": "0.222", "pdb_id": "1Y1D", "reference": "Biochem J. 2005 Jun 1;388(Pt 2):615-21", "keyword": "Transthyretin", "protein_name": "Transthyretin", "ligand_formula": "C13 H7 F2 I O3%%C13 H7 F2 I O3", "peptide_protein_sequence": "chain-ID A: GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE; chain-ID B: GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE", "entry": "S-0074", "length": "127", "uniprot_ac": "P02766", "author": "Gales, L., Macedo-Ribeiro, S., Arsequell, G., Valencia, G., Saraiva, M.J., Damas, A.M.", "ligand_smiles": "c1cc(c(cc1F)F)c2cc(c(c(c2)I)O)C(=O)O%%c1cc(c(cc1F)F)c2cc(c(c(c2)I)O)C(=O)O", "ligand_mw": "376.09%%376.09", "alternative_name": "ATTR, Prealbumin, TBPA", "ligand_name": "2',4'-DIFLUORO-4-HYDROXY-5-IODO-1,1'-BIPHENYL-3-CARBOXYLIC ACID%%2',4'-DIFLUORO-4-HYDROXY-5-IODO-1,1'-BIPHENYL-3-CARBOXYLIC ACID", "pdb_classification": "TRANSPORT PROTEIN", "global_stoichiometry": "Homo 4-mer - A4 ", "inchi_key": "SSYOLLIRAAWGDJ-UHFFFAOYSA-N%%SSYOLLIRAAWGDJ-UHFFFAOYSA-N", "ligand_id": "FHI%%FHI"}