Three-dimensional structures of H-ras p21 mutants: molecular basis for their inability to function as signal switch molecules

Cell. 1990 Aug 10;62(3):539-48. doi: 10.1016/0092-8674(90)90018-a.


The X-ray structures of the guanine nucleotide binding domains (amino acids 1-166) of five mutants of the H-ras oncogene product p21 were determined. The mutations described are Gly-12----Arg, Gly-12----Val, Gln-61----His, Gln-61----Leu, which are all oncogenic, and the effector region mutant Asp-38----Glu. The resolutions of the crystal structures range from 2.0 to 2.6 A. Cellular and mutant p21 proteins are almost identical, and the only significant differences are seen in loop L4 and in the vicinity of the gamma-phosphate. For the Gly-12 mutants the larger side chains interfere with GTP binding and/or hydrolysis. Gln-61 in cellular p21 adopts a conformation where it is able to catalyze GTP hydrolysis. This conformation has not been found for the mutants of Gln-61. Furthermore, Leu-61 cannot activate the nucleophilic water because of the chemical nature of its side chain. The D38E mutation preserves its ability to bind GAP.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Amino Acid Sequence
  • Binding Sites
  • Cell Transformation, Neoplastic*
  • Models, Molecular
  • Mutation*
  • Oncogene Protein p21(ras) / genetics*
  • Protein Conformation
  • X-Ray Diffraction


  • Adenosine Triphosphate
  • Oncogene Protein p21(ras)