title: Structural differences between a ras oncogene protein and the normal protein.
abstract: One of the most commonly found transforming ras oncogenes in human tumours has a valine codon replacing the glycine codon at position 12 of the normal c-Ha-ras gene. To understand the structural reasons behind cell transformation arising from this single amino acid substitution, we have determined the crystal structure of the GDP-bound form of the mutant protein, p21(Val-12), encoded by this oncogene. We report here the overall structure of p21(Val-12) at 2.2 A resolution and compare it with the structure of the normal c-Ha-ras protein. One of the major differences is that the loop of the transforming ras protein that binds the beta-phosphate of the guanine nucleotide is enlarged. Such a change in the 'catalytic site' conformation could explain the reduced GTPase activity of the mutant, which keeps the protein in the GTP bound 'signal on' state for a prolonged period time, ultimately causing cell transformation.
authors.affiliation: Department of Chemistry, University of California, Berkeley 94720.
authors.forename: L A
authors.initials: LA
authors.lastname: Tong
authors.forename: A M
authors.initials: AM
authors.lastname: de Vos
authors.forename: M V
authors.initials: MV
authors.lastname: Milburn
authors.forename: J
authors.initials: J
authors.lastname: Jancarik
authors.forename: S
authors.initials: S
authors.lastname: Noguchi
authors.forename: S
authors.initials: S
authors.lastname: Nishimura
authors.forename: K
authors.initials: K
authors.lastname: Miura
authors.forename: E
authors.initials: E
authors.lastname: Ohtsuka
authors.forename: S H
authors.initials: SH
authors.lastname: Kim
mesh_terms: D003461:Crystallography; D008958:Models, Molecular; D015394:Molecular Structure; D009154:Mutation; D009690:Nucleic Acid Conformation; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras)
chemical_list: D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras)