1zvq
From Proteopedia
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|PDB= 1zvq |SIZE=350|CAPTION= <scene name='initialview01'>1zvq</scene>, resolution 2.0Å | |PDB= 1zvq |SIZE=350|CAPTION= <scene name='initialview01'>1zvq</scene>, resolution 2.0Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=GDP:GUANOSINE-5'-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= HRAS, HRAS1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= HRAS, HRAS1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[4q21|4Q21]], [[1lf5|1LF5]], [[1zw6|1ZW6]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1zvq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zvq OCA], [http://www.ebi.ac.uk/pdbsum/1zvq PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1zvq RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
The flexibility of the conserved 57DTAGQ61 motif is essential for Ras proper cycling in response to growth factors. Here, we increase the flexibility of the 57DTAGQ61 motif by mutating Gln61 to Gly. The crystal structure of the RasQ61G mutant reveals a new conformation of switch 2 that bears remarkable structural homology to an intermediate for GTP hydrolysis revealed by targeted molecular dynamics simulations. The mutation increased retention of GTP and inhibited Ras binding to the catalytic site, but not to the distal site of Sos. Most importantly, the thermodynamics of RafRBD binding to Ras are altered even though the structure of switch 1 is not affected by the mutation. Our results suggest that interplay and transmission of structural information between the switch regions are important factors for Ras function. They propose that initiation of GTP hydrolysis sets off the separation of the Ras/effector complex even before the GDP conformation is reached. | The flexibility of the conserved 57DTAGQ61 motif is essential for Ras proper cycling in response to growth factors. Here, we increase the flexibility of the 57DTAGQ61 motif by mutating Gln61 to Gly. The crystal structure of the RasQ61G mutant reveals a new conformation of switch 2 that bears remarkable structural homology to an intermediate for GTP hydrolysis revealed by targeted molecular dynamics simulations. The mutation increased retention of GTP and inhibited Ras binding to the catalytic site, but not to the distal site of Sos. Most importantly, the thermodynamics of RafRBD binding to Ras are altered even though the structure of switch 1 is not affected by the mutation. Our results suggest that interplay and transmission of structural information between the switch regions are important factors for Ras function. They propose that initiation of GTP hydrolysis sets off the separation of the Ras/effector complex even before the GDP conformation is reached. | ||
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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: Ford, B.]] | [[Category: Ford, B.]] | ||
[[Category: Nassar, N.]] | [[Category: Nassar, N.]] | ||
| - | [[Category: GDP]] | ||
| - | [[Category: MG]] | ||
[[Category: gdp]] | [[Category: gdp]] | ||
[[Category: gtpase]] | [[Category: gtpase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:42:18 2008'' |
Revision as of 22:42, 30 March 2008
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| , resolution 2.0Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | HRAS, HRAS1 (Homo sapiens) | ||||||
| Related: | 4Q21, 1LF5, 1ZW6
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structure of the Q61G mutant of Ras in the GDP-bound form
Overview
The flexibility of the conserved 57DTAGQ61 motif is essential for Ras proper cycling in response to growth factors. Here, we increase the flexibility of the 57DTAGQ61 motif by mutating Gln61 to Gly. The crystal structure of the RasQ61G mutant reveals a new conformation of switch 2 that bears remarkable structural homology to an intermediate for GTP hydrolysis revealed by targeted molecular dynamics simulations. The mutation increased retention of GTP and inhibited Ras binding to the catalytic site, but not to the distal site of Sos. Most importantly, the thermodynamics of RafRBD binding to Ras are altered even though the structure of switch 1 is not affected by the mutation. Our results suggest that interplay and transmission of structural information between the switch regions are important factors for Ras function. They propose that initiation of GTP hydrolysis sets off the separation of the Ras/effector complex even before the GDP conformation is reached.
About this Structure
1ZVQ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure of a transient intermediate for GTP hydrolysis by ras., Ford B, Hornak V, Kleinman H, Nassar N, Structure. 2006 Mar;14(3):427-36. PMID:16531227
Page seeded by OCA on Mon Mar 31 01:42:18 2008
Categories: Homo sapiens | Single protein | Ford, B. | Nassar, N. | Gdp | Gtpase
