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| [[Image:1agp.gif|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_1agp| PDB=1agp | SCENE= }} | | {{STRUCTURE_1agp| PDB=1agp | SCENE= }} |
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| '''THREE-DIMENSIONAL STRUCTURES AND PROPERTIES OF A TRANSFORMING AND A NONTRANSFORMING GLY-12 MUTANT OF P21-H-RAS'''
| | ===THREE-DIMENSIONAL STRUCTURES AND PROPERTIES OF A TRANSFORMING AND A NONTRANSFORMING GLY-12 MUTANT OF P21-H-RAS=== |
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| ==Overview==
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| 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. | | The line below this paragraph, {{ABSTRACT_PUBMED_8357792}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 8357792 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_8357792}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Wittinghofer, A.]] | | [[Category: Wittinghofer, A.]] |
| [[Category: Oncogene protein]] | | [[Category: Oncogene protein]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 10:14:50 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 16:48:39 2008'' |
