821P
THREE-DIMENSIONAL STRUCTURES AND PROPERTIES OF A TRANSFORMING AND A NONTRANSFORMING GLYCINE-12 MUTANT OF P21H-RAS
Summary for 821P
| Entry DOI | 10.2210/pdb821p/pdb |
| Descriptor | C-H-RAS P21 PROTEIN, MAGNESIUM ION, PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER, ... (4 entities in total) |
| Functional Keywords | oncoprotein |
| Biological source | Homo sapiens (human) |
| Cellular location | Cell membrane. Isoform 2: Nucleus: P01112 |
| Total number of polymer chains | 1 |
| Total formula weight | 19461.76 |
| Authors | Scheidig, A.J.,Krengel, U.,Pai, E.F.,Kabsch, W.,Wittinghofer, A.,Goody, R.S. (deposition date: 1993-03-29, release date: 1994-01-31, Last modification date: 2024-02-14) |
| 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 Cited by 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: 8357792DOI: 10.1021/bi00084a005 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.5 Å) |
Structure validation
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