Abstract
The structural effects of amino acid substitutions at positions 12 and 16 in the amino-terminal segment (Tyr 4-Ala 18) of the ras-oncogene-encoded P21 proteins have been investigated using conformational energy analysis. The P21 protein with Val at position 12 and Lys at position 16 is known to have high transforming ability, while the P21 protein with Val at position 12 and Asn at position 16 is known to have poor transforming ability, similar to that of the normal protein (with Gly at 12 and Lys at 16.) The current results demonstrate a significant conformational change at position 15 induced by the substitution of Asn for Lys at position 16, which could explain this alteration in transformation potential. These findings are consistent with previous results suggesting the existence of a normal and a malignancy-causing conformation for the P21 proteins and suggest that the critical transforming region may encompass residues 12–15.
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Brandt-Rauf, P.W., Pincus, M.R., Carty, R.P. et al. Correlation of structure with transforming activity of the P21 proteins with substitutions at positions 12 and 16. J Protein Chem 6, 375–385 (1987). https://doi.org/10.1007/BF02343336
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DOI: https://doi.org/10.1007/BF02343336