521p
From Proteopedia
(New page: 200px<br /> <applet load="521p" size="450" color="white" frame="true" align="right" spinBox="true" caption="521p, resolution 2.6Å" /> '''THREE-DIMENSIONAL ST...) |
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| - | [[Image:521p.gif|left|200px]]<br /> | + | [[Image:521p.gif|left|200px]]<br /><applet load="521p" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="521p" size=" | + | |
caption="521p, resolution 2.6Å" /> | caption="521p, resolution 2.6Å" /> | ||
'''THREE-DIMENSIONAL STRUCTURES OF H-RAS P21 MUTANTS: MOLECULAR BASIS FOR THEIR INABILITY TO FUNCTION AS SIGNAL SWITCH MOLECULES'''<br /> | '''THREE-DIMENSIONAL STRUCTURES OF H-RAS P21 MUTANTS: MOLECULAR BASIS FOR THEIR INABILITY TO FUNCTION AS SIGNAL SWITCH MOLECULES'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The X-ray structures of the guanine nucleotide binding domains (amino | + | 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. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 521P is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG and GTP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 521P is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=GTP:'>GTP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=521P OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Kabsch, W.]] | [[Category: Kabsch, W.]] | ||
[[Category: Krengel, U.]] | [[Category: Krengel, U.]] | ||
| - | [[Category: Pai, E | + | [[Category: Pai, E F.]] |
[[Category: Schlichting, I.]] | [[Category: Schlichting, I.]] | ||
[[Category: Wittinghofer, A.]] | [[Category: Wittinghofer, A.]] | ||
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[[Category: oncogene protein]] | [[Category: oncogene protein]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:14:48 2008'' |
Revision as of 17:14, 21 February 2008
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THREE-DIMENSIONAL STRUCTURES OF H-RAS P21 MUTANTS: MOLECULAR BASIS FOR THEIR INABILITY TO FUNCTION AS SIGNAL SWITCH MOLECULES
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Bladder cancer, somatic OMIM:[190020], Costello syndrome OMIM:[190020], Thyroid carcinoma, follicular, somatic OMIM:[190020]
About this Structure
521P is a Single protein structure of sequence from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
Reference
Three-dimensional structures of H-ras p21 mutants: molecular basis for their inability to function as signal switch molecules., Krengel U, Schlichting I, Scherer A, Schumann R, Frech M, John J, Kabsch W, Pai EF, Wittinghofer A, Cell. 1990 Aug 10;62(3):539-48. PMID:2199064
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