821p: Difference between revisions
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'''THREE-DIMENSIONAL STRUCTURES AND PROPERTIES OF A TRANSFORMING AND A NONTRANSFORMING GLYCINE-12 MUTANT OF P21H-RAS''' | {{Structure | ||
|PDB= 821p |SIZE=350|CAPTION= <scene name='initialview01'>821p</scene>, resolution 1.5Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> and <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER'>GNP</scene> | |||
|ACTIVITY= | |||
|GENE= | |||
}} | |||
'''THREE-DIMENSIONAL STRUCTURES AND PROPERTIES OF A TRANSFORMING AND A NONTRANSFORMING GLYCINE-12 MUTANT OF P21H-RAS''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
821P is a [ | 821P is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=821P OCA]. | ||
==Reference== | ==Reference== | ||
Three-dimensional structures and properties of a transforming and a nontransforming glycine-12 mutant of p21H-ras., Franken SM, Scheidig AJ, Krengel U, Rensland H, Lautwein A, Geyer M, Scheffzek K, Goody RS, Kalbitzer HR, Pai EF, et al., Biochemistry. 1993 Aug 24;32(33):8411-20. PMID:[http:// | Three-dimensional structures and properties of a transforming and a nontransforming glycine-12 mutant of p21H-ras., Franken SM, Scheidig AJ, Krengel U, Rensland H, Lautwein A, Geyer M, Scheffzek K, Goody RS, Kalbitzer HR, Pai EF, et al., Biochemistry. 1993 Aug 24;32(33):8411-20. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8357792 8357792] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: oncogene protein]] | [[Category: oncogene protein]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 19:15:11 2008'' | ||
Revision as of 20:15, 20 March 2008
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| Coordinates: | save as pdb, mmCIF, xml | ||||||
THREE-DIMENSIONAL STRUCTURES AND PROPERTIES OF A TRANSFORMING AND A NONTRANSFORMING GLYCINE-12 MUTANT OF P21H-RAS
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Bladder cancer, somatic OMIM:[190020], Costello syndrome OMIM:[190020], Thyroid carcinoma, follicular, somatic OMIM:[190020]
About this StructureAbout this Structure
821P is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Three-dimensional structures and properties of a transforming and a nontransforming glycine-12 mutant of p21H-ras., Franken SM, Scheidig AJ, Krengel U, Rensland H, Lautwein A, Geyer M, Scheffzek K, Goody RS, Kalbitzer HR, Pai EF, et al., Biochemistry. 1993 Aug 24;32(33):8411-20. PMID:8357792
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