1he8: Difference between revisions

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[[Image:1he8.gif|left|200px]]<br /><applet load="1he8" size="350" color="white" frame="true" align="right" spinBox="true"
[[Image:1he8.gif|left|200px]]
caption="1he8, resolution 3.00&Aring;" />
 
'''RAS G12V-PI 3-KINASE GAMMA COMPLEX'''<br />
{{Structure
|PDB= 1he8 |SIZE=350|CAPTION= <scene name='initialview01'>1he8</scene>, resolution 3.00&Aring;
|SITE= <scene name='pdbsite=AC1:Mg+Binding+Site+For+Chain+C'>AC1</scene> and <scene name='pdbsite=AC2:Gnp+Binding+Site+For+Chain+C'>AC2</scene>
|LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> and <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER'>GNP</scene>
|ACTIVITY= [http://en.wikipedia.org/wiki/Phosphatidylinositol_3-kinase Phosphatidylinositol 3-kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.137 2.7.1.137]
|GENE=
}}
 
'''RAS G12V-PI 3-KINASE GAMMA COMPLEX'''
 


==Overview==
==Overview==
Line 10: Line 19:


==About this Structure==
==About this Structure==
1HE8 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=GNP:'>GNP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Phosphatidylinositol_3-kinase Phosphatidylinositol 3-kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.137 2.7.1.137] Known structural/functional Sites: <scene name='pdbsite=AC1:Mg+Binding+Site+For+Chain+C'>AC1</scene> and <scene name='pdbsite=AC2:Gnp+Binding+Site+For+Chain+C'>AC2</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HE8 OCA].  
1HE8 is a [[Protein complex]] structure of sequences 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=1HE8 OCA].  


==Reference==
==Reference==
Crystal structure and functional analysis of Ras binding to its effector phosphoinositide 3-kinase gamma., Pacold ME, Suire S, Perisic O, Lara-Gonzalez S, Davis CT, Walker EH, Hawkins PT, Stephens L, Eccleston JF, Williams RL, Cell. 2000 Dec 8;103(6):931-43. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11136978 11136978]
Crystal structure and functional analysis of Ras binding to its effector phosphoinositide 3-kinase gamma., Pacold ME, Suire S, Perisic O, Lara-Gonzalez S, Davis CT, Walker EH, Hawkins PT, Stephens L, Eccleston JF, Williams RL, Cell. 2000 Dec 8;103(6):931-43. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11136978 11136978]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Phosphatidylinositol 3-kinase]]
[[Category: Phosphatidylinositol 3-kinase]]
Line 43: Line 52:
[[Category: second messenger generation]]
[[Category: second messenger generation]]


''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:00:21 2008''
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:35:56 2008''

Revision as of 09:35, 20 March 2008

File:1he8.gif


Drag the structure with the mouse to rotate
1he8, resolution 3.00Å
Sites: AC1 and AC2
Ligands: MG and GNP
Activity: Phosphatidylinositol 3-kinase, with EC number 2.7.1.137
Coordinates: save as pdb, mmCIF, xml



RAS G12V-PI 3-KINASE GAMMA COMPLEX


Overview

Ras activation of phosphoinositide 3-kinase (PI3K) is important for survival of transformed cells. We find that PI3Kgamma is strongly and directly activated by H-Ras G12V in vivo or by GTPgammaS-loaded H-Ras in vitro. We have determined a crystal structure of a PI3Kgamma/Ras.GMPPNP complex. A critical loop in the Ras binding domain positions Ras so that it uses its switch I and switch II regions to bind PI3Kgamma. Mutagenesis shows that interactions with both regions are essential for binding PI3Kgamma. Ras also forms a direct contact with the PI3Kgamma catalytic domain. These unique Ras/PI3Kgamma interactions are likely to be shared by PI3Kalpha. The complex with Ras shows a change in the PI3K conformation that may represent an allosteric component of Ras activation.

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

1HE8 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Crystal structure and functional analysis of Ras binding to its effector phosphoinositide 3-kinase gamma., Pacold ME, Suire S, Perisic O, Lara-Gonzalez S, Davis CT, Walker EH, Hawkins PT, Stephens L, Eccleston JF, Williams RL, Cell. 2000 Dec 8;103(6):931-43. PMID:11136978

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