title: Solution structure and ligand-binding site of the SH3 domain of the p85 alpha subunit of phosphatidylinositol 3-kinase.
abstract: SH3 domains are found in proteins associated with receptor tyrosine kinase signal transduction complexes. The solution structure of the SH3 domain of the 85 kd regulatory subunit of phosphatidylinositol 3-kinase is shown to be a compact beta barrel consisting of five beta strands arranged in two beta sheets of three and two strands. The structure is similar to that of chicken brain alpha spectrin but represents a distinct class of SH3 domain, with an insertion between the second and third beta strands that may influence binding specificity. 1H chemical shift changes induced by complex formation with a synthetic peptide derived from the SH3-binding protein dynamin, together with amino acid sequence comparisons, suggest that the ligand-binding site consists of a hydrophobic surface flanked by two charged loops.
authors.affiliation: Department of Biochemistry, University of Oxford, England.
authors.forename: G W
authors.initials: GW
authors.lastname: Booker
authors.forename: I
authors.initials: I
authors.lastname: Gout
authors.forename: A K
authors.initials: AK
authors.lastname: Downing
authors.forename: P C
authors.initials: PC
authors.lastname: Driscoll
authors.forename: J
authors.initials: J
authors.lastname: Boyd
authors.forename: M D
authors.initials: MD
authors.lastname: Waterfield
authors.forename: I D
authors.initials: ID
authors.lastname: Campbell
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D034281:Dynamins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019869:Phosphatidylinositol 3-Kinases; D010770:Phosphotransferases / Q000737:chemistry*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D013049:Spectrin / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D013049:Spectrin; D010770:Phosphotransferases; D019869:Phosphatidylinositol 3-Kinases; D016392:Proto-Oncogene Proteins pp60(c-src); D017301:Ca(2+) Mg(2+)-ATPase; D034281:Dynamins