1zvq

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|PDB= 1zvq |SIZE=350|CAPTION= <scene name='initialview01'>1zvq</scene>, resolution 2.0&Aring;
|PDB= 1zvq |SIZE=350|CAPTION= <scene name='initialview01'>1zvq</scene>, resolution 2.0&Aring;
|SITE=
|SITE=
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|LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> and <scene name='pdbligand=GDP:GUANOSINE-5'-DIPHOSPHATE'>GDP</scene>
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|LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> and <scene name='pdbligand=GDP:GUANOSINE-5&#39;-DIPHOSPHATE'>GDP</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])
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[[Category: gtpase]]
[[Category: gtpase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:40:24 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 23 14:31:43 2008''

Revision as of 12:31, 23 March 2008

Image:1zvq.gif


PDB ID 1zvq

Drag the structure with the mouse to rotate
, resolution 2.0Å
Ligands: and
Gene: HRAS, HRAS1 (Homo sapiens)
Coordinates: save as pdb, mmCIF, xml



Structure of the Q61G mutant of Ras in the GDP-bound form


Contents

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.

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

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

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