Three-dimensional structure of p21 in the active conformation and analysis of an oncogenic mutant.
The three-dimensional structure of the active guanosine triphosphate (GTP)-analogue-containing complex of the H-ras-encoded p21 has been determined. It was necessary to correct the topology of p21 as published earlier. The structure analysis shows all of the interactions between protein and GTP and how the important cofactor Mg2+ is bound. From the oncogenic mutants of p21 crystallized, a Gly12 to Arg mutation has been analyzed in detail. It shows that the overall structure of the mutant is not perturbed and that the side chain of Arg12 is coming close to the gamma-phosphate for an interaction.
Wittinghofer
F
F
Max-Planck-Institut für Medizinische Forschung, Abteilung Biophysik, Heidelberg, Germany.
Krengel
U
U
John
J
J
Kabsch
W
W
Pai
E F
EF
D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D001665:Binding Sites; D004789:Enzyme Activation; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D020690:GTPase-Activating Proteins; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D008274:Magnesium / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014961:X-Ray Diffraction; D020703:ras GTPase-Activating Proteins
D020690:GTPase-Activating Proteins; D011506:Proteins; D020703:ras GTPase-Activating Proteins; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D020558:GTP Phosphohydrolases; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D008274:Magnesium