{"method": "X-RAY DIFFRACTION", "mutation_s_field": "No", "ec_number": "", "description": "A main finding of this investigation was the highly preferential binding of resveratrol and thyroxine, both characterized by negative binding cooperativity, to distinct sites in TTR, consistent with the data of x-ray analysis of TTR in complex with both ligands. Although revealing the ability of the two thyroxine binding sites of TTR to discriminate between different ligands, this feature has allowed us to evaluate the interactions of polyphenols with both resveratrol and thyroxine preferential binding sites. Among flavonoids, genistein and apigenin were able to effectively displace resveratrol from its preferential binding site, whereas genistein also showed the ability to interact, albeit weakly, with the preferential thyroxine binding site. Several glucuronidated polyphenol metabolites did not exhibit significant competition for resveratrol and thyroxine preferential binding sites and lacked the ability to stabilize TTR. However, resveratrol-3-O-sulfate was able to significantly protect the protein native state.", "ligstr": "T44:A:C15 H11 I4 N O4:776.87:3,5,3',5'-TETRAIODO-L-THYRONINE:c1c(cc(c(c1I)Oc2cc(c(c(c2)I)O)I)I)C[C@@H](C(=O)O)N:InChI=1S/C15H11I4NO4/c16-8-4-7(5-9(17)13(8)21)24-14-10(18)1-6(2-11(14)19)3-12(20)15(22)23/h1-2,4-5,12,21H,3,20H2,(H,22,23)/t12-/m0/s1:XUIIKFGFIJCVMT-LBPRGKRZSA-N;STL:B:C14 H12 O3:228.24:RESVERATROL:c1cc(ccc1C=Cc2cc(cc(c2)O)O)O:InChI=1S/C14H12O3/c15-12-5-3-10(4-6-12)1-2-11-7-13(16)9-14(17)8-11/h1-9,15-17H/b2-1+:LUKBXSAWLPMMSZ-OWOJBTEDSA-N", "pmid": "26468275", "remarks": "Crystal structure of TTR/resveratrol/T4 complex", "amyloid_non_amyloid": "Non-amyloid", "type": "Inhibitor complex", "inchi": "InChI=1S/C15H11I4NO4/c16-8-4-7(5-9(17)13(8)21)24-14-10(18)1-6(2-11(14)19)3-12(20)15(22)23/h1-2,4-5,12,21H,3,20H2,(H,22,23)/t12-/m0/s1%%InChI=1S/C14H12O3/c15-12-5-3-10(4-6-12)1-2-11-7-13(16)9-14(17)8-11/h1-9,15-17H/b2-1+", "resolution": "1.54", "species": "Homo sapiens", "secondary_structure": "CPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGSSPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNP#CCEEEEEEETTTTEECCSCEEEEEEECTTSCEEEEEEEECCTTSEECCSCCTTTCCSEEEEEEECHHHHHHHTTCCCSEEEEEEEEEESTTSCCEEEEEEEEETTEEEEEEEEECC&CPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGSSPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNP#CCEEEEEEETTTTEECTTCEEEEEEECTTSCEEEEEEEECCTTSEECCSCCTTTCCSEEEEEEECHHHHHHHTTCCCSEEEEEEEEEECTTSCSEEEEEEEEETTEEEEEEEEECC", "chain_id": "A%%B", "gene_names": "TTR, PALB", "r_value_free": "0.193", "pdb_id": "5CR1", "reference": "J Biol Chem. 2015 Dec 11;290(50):29769-80.", "keyword": "Transthyretin", "protein_name": "Transthyretin", "ligand_formula": "C15 H11 I4 N O4%%C14 H12 O3", "peptide_protein_sequence": "chain-ID A: CPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGSSPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNP; chain-ID B: CPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGSSPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNP", "entry": "S-0422", "length": "116", "uniprot_ac": "P02766", "author": "Florio, P., Folli, C., Cianci, M., Del Rio, D., Zanotti, G., Berni, R.", "ligand_smiles": "c1c(cc(c(c1I)Oc2cc(c(c(c2)I)O)I)I)C[C@@H](C(=O)O)N%%c1cc(ccc1C=Cc2cc(cc(c2)O)O)O", "ligand_mw": "776.87%%228.24", "alternative_name": "ATTR, Prealbumin, TBPA", "ligand_name": "3,5,3',5'-TETRAIODO-L-THYRONINE%%RESVERATROL", "pdb_classification": "TRANSPORT PROTEIN", "global_stoichiometry": "Homo 4-mer - A4 ", "inchi_key": "XUIIKFGFIJCVMT-LBPRGKRZSA-N%%LUKBXSAWLPMMSZ-OWOJBTEDSA-N", "ligand_id": "T44%%STL"}