1AGP

THREE-DIMENSIONAL STRUCTURES AND PROPERTIES OF A TRANSFORMING AND A NONTRANSFORMING GLY-12 MUTANT OF P21-H-RAS

Summary for 1AGP

• Entry DOI: 10.2210/pdb1agp/pdb
• Descriptor: C-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: 19479.73

Authors

Franken, S.M.,Scheidig, A.J.,Wittinghofer, A.,Goody, R.S. (deposition date: 1993-03-29, release date: 1994-04-30, Last modification date: 2024-02-07)

Primary citation

Franken, S.M.,Scheidig, A.J.,Krengel, U.,Rensland, H.,Lautwein, A.,Geyer, M.,Scheffzek, K.,Goody, R.S.,Kalbitzer, H.R.,Pai, E.F.,Wittinghofer, A.
Three-dimensional structures and properties of a transforming and a nontransforming glycine-12 mutant of p21H-ras.
Biochemistry, 32:8411-8420, 1993

PubMed Abstract: The three-dimensional structures and biochemical properties of two mutants of the G-domain (residues 1-166) of p21H-ras, p21 (G12D) and p21 (G12P), have been determined in the triphosphate-bound form using guanosine 5'-(beta,gamma-imido)triphosphate (GppNHp). They correspond to the most frequent oncogenic and the only nononcogenic mutation of Gly-12, respectively. The G12D mutation is the only mutant analyzed so far that crystallizes in a space group different from wild type, and the atomic model of the protein shows the most drastic changes of structure around the active site as compared to wild-type p21. This is due to the interactions of the aspartic acid side chain with Tyr-32, Gln-61, and the gamma-phosphate, which result in reduced mobility of these structural elements. The interaction between the carboxylate group of Asp-12 and the gamma-phosphate is mediated by a shared proton, which we show by 31P NMR measurements to exist in solution as well. The structure of p21 (G12P) is remarkably similar to that of wild-type p21 in the active site, including the position of the nucleophilic water. The pyrrolidine ring of Pro-12 points outward and seems to be responsible for the weaker affinity toward GAP (GTPase-activating protein) and the failure of GAP to stimulate GTP hydrolysis.

PubMed: 8357792
DOI: 10.1021/bi00084a005

Experimental method

X-RAY DIFFRACTION (2.3 Å)