An activating amino acid substitution in the c-abl oncogene protein fails to produce a local conformational change

J Protein Chem. 1991 Aug;10(4):437-41. doi: 10.1007/BF01025258.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Cell Transformation, Neoplastic
  • Genes, abl / genetics*
  • Glutamates
  • Humans
  • Lysine
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Oncogene Proteins / chemistry*
  • Oncogene Proteins / genetics*
  • Philadelphia Chromosome
  • Protein Conformation
  • Software

Substances

  • Glutamates
  • Oncogene Proteins
  • Lysine