title: The three-dimensional structure of the first EGF-like module of human factor IX: comparison with EGF and TGF-alpha.
abstract: The three-dimensional structure of the first epidermal growth factor (EGF)-like module from human factor IX has been determined in solution using two-dimensional nuclear magnetic resonance (in the absence of calcium and at pH 4.5). The structure was found to resemble closely that of EGF and the homologous transforming growth factor-alpha (TGF-alpha). Residues 60-65 form an antiparallel beta-sheet with residues 68-73. In the C-terminal subdomain a type II beta-turn is found between residues 74 and 77 and a five-residue turn is found between residues 79 and 83. Glu 78 and Leu 84 pair in an antiparallel beta-sheet conformation. In the N-terminal region a loop is found between residues 50 and 55 such that the side chains of both are positioned above the face of the beta-sheet. Residues 56-60 form a turn that leads into the first strand of the beta-sheet. Whereas the global fold closely resembles that of EGF, the N-terminal residues of the module (46-49) do not form a beta-strand but are ill-defined in the structure, probably due to the local flexibility of this region. The structure is discussed with reference to recent site-directed mutagenesis data, which have identified certain conserved residues as ligands for calcium.
authors.affiliation: Department of Biochemistry, University of Oxford, UK.
authors.forename: M
authors.initials: M
authors.lastname: Baron
authors.forename: D G
authors.initials: DG
authors.lastname: Norman
authors.forename: T S
authors.initials: TS
authors.lastname: Harvey
authors.forename: P A
authors.initials: PA
authors.lastname: Handford
authors.forename: M
authors.initials: M
authors.lastname: Mayhew
authors.forename: A G
authors.initials: AG
authors.lastname: Tse
authors.forename: G G
authors.initials: GG
authors.lastname: Brownlee
authors.forename: I D
authors.initials: ID
authors.lastname: Campbell
mesh_terms: D000595:Amino Acid Sequence; D002118:Calcium / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000737:chemistry* / Q000378:metabolism; D005164:Factor IX / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; D005164:Factor IX; D002118:Calcium