title: Three-dimensional structure and properties of wild-type and mutant H-ras-encoded p21.
abstract: Ras (or p21) is the product of the ras proto-oncogene and is believed to be involved in growth-promoting signal transduction. The structure of the guanine nucleotide-binding domain of H-Ras (or p21H-ras) in the triphosphate conformation was determined at very high resolution (1.4 A). All the binding interactions between protein and Gpp[NH]p and Mg2+ can be resolved in great detail. The region around amino acids 61-65 is flexible and exists in two conformations, one of which seems to be important for catalysis. The properties and structures of several oncogenic and non-oncogenic mutant forms of Ras have also been determined. Since the structure of the GDP-bound form is also known, the nature of the conformational change from the GTP-bound to the GDP-bound form can be inferred from the 3-D structure. A mechanism for the intrinsic GTP hydrolysis has been proposed. Its implications for the GAP-stimulated GTPase reaction is discussed in the light of recent kinetic and mutational experiments.
authors.affiliation: Max Planck Institute for Medical Research, Heidelberg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Wittinghofer
authors.forename: S M
authors.initials: SM
authors.lastname: Franken
authors.forename: A J
authors.initials: AJ
authors.lastname: Scheidig
authors.forename: H
authors.initials: H
authors.lastname: Rensland
authors.forename: A
authors.initials: A
authors.lastname: Lautwein
authors.forename: E F
authors.initials: EF
authors.lastname: Pai
authors.forename: R S
authors.initials: RS
authors.lastname: Goody
mesh_terms: D000818:Animals; D020558:GTP Phosphohydrolases / Q000378:metabolism; D011905:Genes, ras; D005815:Genetic Code; D006801:Humans; D009154:Mutation; D011487:Protein Conformation; D000090063:Proto-Oncogene Mas; D016283:Proto-Oncogene Proteins p21(ras) / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D020558:GTP Phosphohydrolases; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)