{"resolution": "1.7", "ligand_mw": "", "secondary_structure": "GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE#CCCCCCCCCCCEEEEEEETTTTEECTTCEEEEEEECTTSCEEEEEEEECCTTSEECCSCCTTTCCSEEEEEEECHHHHHHHHTCCCSEEEEEEEEEESTTSCCEEEEEEEEETTEEEEEEEEECCCC&GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE#CCCCCCCCCCCEEEEEEETTTTEECCSCEEEEEEECCCCCEEEEEEEECCTTSEECCSCCTTTCCSEEEEEEEECCCCCCCCCCCCCCEEEEEEEEECCCCCCCEEEEEEEETTEEEEEEEECCCCC", "inchi": "", "method": "X-RAY DIFFRACTION", "ec_number": "", "uniprot_ac": "P02766", "remarks": "Crystal structure of human Transthyretin (TTR) at pH3.5", "description": "To investigate the influence of acidification on the quaternary and tertiary structures of TTR, crystal structures of wild-type human TTR at pH 4.0 and pH 3.5 have been determined. The pH 4.0 crystal structure reveals that the native fold of the tetramer remains mostly undisturbed. In particular, subunit A of the TTR pH 4.0 structure is very similar to the wild-type TTR pH 7.4 structure with an r.m.s.d. of 0.38 A. In contrast, subunit B of the TTR pH 4.0 structure exhibits several significant changes. The EF-helix (residues 75-81) and the adjacent EF-loop (residues 82-90) show an r.m.s.d. greater than 2.0 A. The acidic residues within this region (Glu72, Asp74, Glu89, and Glu92) undergo significant conformational changes that instigate movement of the EF helix-loop region and make residues Lys70, Lys76, His88, and His90 orient their side chains toward these acidic residues. In particular, Glu89 undergoes a maximum deviation of 5.6 A, occupying Phe87's initial position in the wild-type TTR pH 7.4 structure, and points its side chain into a hydrophobic pocket of the neighboring subunit. These results demonstrate that acidic conditions increase the susceptibility of the EF helix-loop region of the TTR B subunit to undergo conformational changes and unfold, likely destabilizing the tetramer and identifying at least the initial conformational changes likely occurring within the tetramer that leads to the amyloidogenic monomer.", "type": "Protein", "ligand_smiles": "", "chain_id": "", "species": "Homo sapiens", "keyword": "Transthyretin", "ligstr": "", "pmid": "18662699", "mutation_s_field": "No", "author": "Palaninathan, S.K., Mohamedmohaideen, N.N., Snee, W.C., Kelly, J.W., Sacchettini, J.C.", "pdb_id": "3CBR", "amyloid_non_amyloid": "Amyloid", "inchi_key": "", "ligand_name": "", "ligand_formula": "", "ligand_id": "", "r_value_free": "0.26", "protein_name": "Transthyretin", "gene_names": "TTR, PALB", "global_stoichiometry": "Homo 4-mer - A4 ", "alternative_name": "ATTR, Prealbumin, TBPA", "peptide_protein_sequence": "chain-ID A: GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE; chain-ID B: GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE", "pdb_classification": "THYROXINE BINDING PROTEIN", "reference": "J Mol Biol. 2008 Oct 24;382(5):1157-67.", "length": "127", "entry": "S-0193"}