Prediction of the three-dimensional structure of the transforming region of the EJ/T24 human bladder oncogene product and its normal cellular homologue.

Abstract

The 3-dimensional structures of the transforming region of the product of the EJ/T24 human bladder oncogene and of the c-Ha ras-1 gene product were calculated by using conformational energy calculations. These 2 genes, representing a transforming oncogene and its normal cellular homologue, encode 21,000-dalton peptides that differ by 1 amino acid at position 12. The energetically allowed conformations of the hydrophobic decapeptide surrounding this substitution site were examined. The calculations show that the most favorable form of the c-Ha ras-1 gene product exists when Gly-12 is in a left-handed bend conformation. No other amino acid can adopt this conformation and thus the bladder oncogene peptide containing valine at position 12 has a markedly different 3-dimensional structure. A simple model is proposed to account for the consequences of a position 12 mutation.