421P

THREE-DIMENSIONAL STRUCTURES OF H-RAS P21 MUTANTS: MOLECULAR BASIS FOR THEIR INABILITY TO FUNCTION AS SIGNAL SWITCH MOLECULES

Summary for 421P

• Entry DOI: 10.2210/pdb421p/pdb
• Descriptor: H-RAS P21 PROTEIN, MAGNESIUM ION, PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER, ... (4 entities in total)
• Functional Keywords: oncogene protein
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane. Isoform 2: Nucleus: P01112
• Total number of polymer chains: 1
• Total formula weight: 19521.83

Authors

Krengel, U.,John, J.,Scherer, A.,Kabsch, W.,Wittinghofer, A.,Pai, E.F. (deposition date: 1991-06-06, release date: 1994-01-31, Last modification date: 2024-02-28)

Primary citation

Krengel, U.,Schlichting, I.,Scherer, A.,Schumann, R.,Frech, M.,John, J.,Kabsch, W.,Pai, E.F.,Wittinghofer, A.
Three-dimensional structures of H-ras p21 mutants: molecular basis for their inability to function as signal switch molecules.
Cell(Cambridge,Mass.), 62:539-548, 1990

PubMed Abstract: 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.

PubMed: 2199064
DOI: 10.1016/0092-8674(90)90018-A

Experimental method

X-RAY DIFFRACTION (2.2 Å)