1lf0
From Proteopedia
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|PDB= 1lf0 |SIZE=350|CAPTION= <scene name='initialview01'>1lf0</scene>, resolution 1.70Å | |PDB= 1lf0 |SIZE=350|CAPTION= <scene name='initialview01'>1lf0</scene>, resolution 1.70Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[5p21|5P21]], [[1lf5|1LF5]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1lf0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lf0 OCA], [http://www.ebi.ac.uk/pdbsum/1lf0 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1lf0 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
The conformational changes in Ras that accompany the hydrolysis of GTP are critical to its function as a molecular switch in signaling pathways. Understanding how GTP is hydrolyzed by revealing the sequence of intermediary structures in the reaction is essential for understanding Ras signaling. Until now, no structure of an intermediate in GTP hydrolysis has been experimentally determined for Ras alone. We have solved the crystal structure of the Ala-59 to Gly mutant of Ras, (RasA59G), bound to guanosine 5'-imidotriphosphate or GDP to 1.7-A resolution. In the guanosine 5'-imidotriphosphate-bound form, this mutant adopts a conformation that is intermediate between the GTP- and GDP-bound forms of wild-type Ras and that is similar to what has been predicted by molecular dynamics simulation [Ma, J. P. & Karplus, M. (1997) Proc. Natl. Acad. Sci. USA 94, 11905-11910]. This conformation is stabilized by direct and water-mediated interactions between the switch 1 and switch 2 regions and is characterized by an increase in the binding affinity for GTP. We propose that the structural changes promoted by the Ala-59 to Gly mutation exhibit a discrete conformational state assumed by wild-type Ras during GTP hydrolysis. | The conformational changes in Ras that accompany the hydrolysis of GTP are critical to its function as a molecular switch in signaling pathways. Understanding how GTP is hydrolyzed by revealing the sequence of intermediary structures in the reaction is essential for understanding Ras signaling. Until now, no structure of an intermediate in GTP hydrolysis has been experimentally determined for Ras alone. We have solved the crystal structure of the Ala-59 to Gly mutant of Ras, (RasA59G), bound to guanosine 5'-imidotriphosphate or GDP to 1.7-A resolution. In the guanosine 5'-imidotriphosphate-bound form, this mutant adopts a conformation that is intermediate between the GTP- and GDP-bound forms of wild-type Ras and that is similar to what has been predicted by molecular dynamics simulation [Ma, J. P. & Karplus, M. (1997) Proc. Natl. Acad. Sci. USA 94, 11905-11910]. This conformation is stabilized by direct and water-mediated interactions between the switch 1 and switch 2 regions and is characterized by an increase in the binding affinity for GTP. We propose that the structural changes promoted by the Ala-59 to Gly mutation exhibit a discrete conformational state assumed by wild-type Ras during GTP hydrolysis. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Bladder cancer, somatic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=190020 190020]], Costello syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=190020 190020]], Thyroid carcinoma, follicular, somatic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=190020 190020]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Hall, B E.]] | [[Category: Hall, B E.]] | ||
[[Category: Nassar, N.]] | [[Category: Nassar, N.]] | ||
| - | [[Category: CA]] | ||
| - | [[Category: GNP]] | ||
| - | [[Category: MG]] | ||
[[Category: gtp]] | [[Category: gtp]] | ||
[[Category: gtpase]] | [[Category: gtpase]] | ||
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[[Category: ra]] | [[Category: ra]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:02:02 2008'' |
Revision as of 19:02, 30 March 2008
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| , resolution 1.70Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||
| Related: | 5P21, 1LF5
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of RasA59G in the GTP-bound form
Overview
The conformational changes in Ras that accompany the hydrolysis of GTP are critical to its function as a molecular switch in signaling pathways. Understanding how GTP is hydrolyzed by revealing the sequence of intermediary structures in the reaction is essential for understanding Ras signaling. Until now, no structure of an intermediate in GTP hydrolysis has been experimentally determined for Ras alone. We have solved the crystal structure of the Ala-59 to Gly mutant of Ras, (RasA59G), bound to guanosine 5'-imidotriphosphate or GDP to 1.7-A resolution. In the guanosine 5'-imidotriphosphate-bound form, this mutant adopts a conformation that is intermediate between the GTP- and GDP-bound forms of wild-type Ras and that is similar to what has been predicted by molecular dynamics simulation [Ma, J. P. & Karplus, M. (1997) Proc. Natl. Acad. Sci. USA 94, 11905-11910]. This conformation is stabilized by direct and water-mediated interactions between the switch 1 and switch 2 regions and is characterized by an increase in the binding affinity for GTP. We propose that the structural changes promoted by the Ala-59 to Gly mutation exhibit a discrete conformational state assumed by wild-type Ras during GTP hydrolysis.
About this Structure
1LF0 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The structural basis for the transition from Ras-GTP to Ras-GDP., Hall BE, Bar-Sagi D, Nassar N, Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12138-42. Epub 2002 Sep 4. PMID:12213964
Page seeded by OCA on Sun Mar 30 22:02:02 2008
Categories: Homo sapiens | Single protein | Bar-Sagi, D. | Hall, B E. | Nassar, N. | Gtp | Gtpase | Intermediate | Ra
