title: An activating amino acid substitution in the c-abl oncogene protein fails to produce a local conformational change.
abstract: The bcr-abl chimeric gene of Philadelphia chromosome positive chronic myelogenous leukemias is only weakly transforming. This transformation activity is greatly enhanced by a Lys-for-Glu substitution at position 832 in the c-abl gene, as occurs in the highly transforming v-abl genes. It has been suggested that this mutation results in a significant structural change in the encoded protein product. Using conformational energy analysis, we have determined the allowed low-energy conformations for residues 828-836 of this protein with Lys and Glu at position 832. In both cases, the overwhelmingly preferred conformation for this region is a bend-helix motif. The helix terminates at residue 836, and there are no discernible differences in conformation between the Lys- and Glu-containing sequences. These results suggest that the activating amino acid substitution at position 832 in the c-abl protein product does not produce its effect via a local conformational change.
authors.affiliation: Department of Medicine, Columbia-Presbyterian Medical Center, New York, New York 10032.
authors.forename: P W
authors.initials: PW
authors.lastname: Brandt-Rauf
authors.forename: G
authors.initials: G
authors.lastname: Bomzer
authors.forename: D
authors.initials: D
authors.lastname: Belford
authors.forename: M R
authors.initials: MR
authors.lastname: Pincus
mesh_terms: D000595:Amino Acid Sequence; D002471:Cell Transformation, Neoplastic; D016313:Genes, abl / Q000235:genetics*; D005971:Glutamates; D006801:Humans; D008239:Lysine; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D015513:Oncogene Proteins / Q000737:chemistry* / Q000235:genetics*; D010677:Philadelphia Chromosome; D011487:Protein Conformation; D012984:Software
chemical_list: D005971:Glutamates; D015513:Oncogene Proteins; D008239:Lysine