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1he8
From Proteopedia
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| - | [[Image:1he8.gif|left|200px]]<br /><applet load="1he8" size=" | + | [[Image:1he8.gif|left|200px]]<br /><applet load="1he8" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1he8, resolution 3.00Å" /> | caption="1he8, resolution 3.00Å" /> | ||
'''RAS G12V-PI 3-KINASE GAMMA COMPLEX'''<br /> | '''RAS G12V-PI 3-KINASE GAMMA COMPLEX'''<br /> | ||
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==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 MG and GNP 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:// | + | 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]. |
==Reference== | ==Reference== | ||
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[[Category: second messenger generation]] | [[Category: second messenger generation]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 09:48:50 2008'' |
Revision as of 07:48, 3 February 2008
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RAS G12V-PI 3-KINASE GAMMA COMPLEX
Contents |
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 with and as ligands. Active as Phosphatidylinositol 3-kinase, with EC number 2.7.1.137 Known structural/functional Sites: and . 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
Page seeded by OCA on Sun Feb 3 09:48:50 2008
Categories: Homo sapiens | Phosphatidylinositol 3-kinase | Protein complex | Davis, C.T. | Eccleston, J.F. | Hawkins, P.T. | Lara-Gonzalez, S. | Pacold, M.E. | Perisic, O. | Stephens, L. | Suire, S. | Walker, E.H. | Williams, R.L. | GNP | MG | Gmppnp | Gtp | H-ras g12v | Heat domain | Oncogene protein | Phosphoinositide 3-kinase gamma - h-ras g12v complex | Pi 3-k | Pi 3-kinase | Pi3k | Ras effector | Ras-binding domain | Second messenger generation
