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The Three-Dimensional Structure of P21 in the Catalytically Active Conformation and Analysis of Oncogenic Mutants

  • Ute Krengel
  • Ilme Schlichting
  • Axel Scheidig
  • Matthias Frech
  • Jacob John
  • Alfred Lautwein
  • Fred Wittinghofer
  • Wolfgang Kabsch
  • Emil F. Pai
Part of the NATO ASI Series book series (NSSA, volume 220)

Summary

The three-dimensional crystal structure of the catalytically active, GTP-analogue containing complex of H-ras encoded p21 (aa 1–166) has been determined at 1.35 Å resolution. It has the same topology as the G-binding domain of elongation factor Tu. The structure analysis revealed the binding sites of the nucleotide and of the essential cofactor Mg2+ in great detail and made it possible to propose a mechanism for GTP hydrolysis. In addition to the wild-type protein, the structures of several p21 mutants have been solved. While the overall structures of these proteins are not perturbed, there are small, but significant differences at the positions of the mutated amino acids. In the oncogenic mutants (Gly-12→Arg, Gly-12→Val, Gln-61→Leu, Gln-61→His), these mutations interfere with the proposed mechanism of catalysis and thus lead to a reduced rate of GTP hydrolysis.

Keywords

Phosphate Binding Oncogenic Mutant Aliphatic Side Chain Guanine Base Phosphate Oxygen 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Ute Krengel
    • 1
  • Ilme Schlichting
    • 1
  • Axel Scheidig
    • 1
  • Matthias Frech
    • 1
  • Jacob John
    • 1
  • Alfred Lautwein
    • 1
  • Fred Wittinghofer
    • 1
  • Wolfgang Kabsch
    • 1
  • Emil F. Pai
    • 1
  1. 1.Abteilung BiophysikMax-Planck-Institut für medizinische ForschungHeidelbergGermany

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