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1he8
From Proteopedia
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|PDB= 1he8 |SIZE=350|CAPTION= <scene name='initialview01'>1he8</scene>, resolution 3.00Å | |PDB= 1he8 |SIZE=350|CAPTION= <scene name='initialview01'>1he8</scene>, resolution 3.00Å | ||
|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> | |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= | + | |LIGAND= <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1he8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1he8 OCA], [http://www.ebi.ac.uk/pdbsum/1he8 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1he8 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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:[[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: Walker, E H.]] | [[Category: Walker, E H.]] | ||
[[Category: Williams, R L.]] | [[Category: Williams, R L.]] | ||
| - | [[Category: GNP]] | ||
| - | [[Category: MG]] | ||
[[Category: gmppnp]] | [[Category: gmppnp]] | ||
[[Category: gtp]] | [[Category: gtp]] | ||
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[[Category: second messenger generation]] | [[Category: second messenger generation]] | ||
| - | ''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 21:03:20 2008'' |
Revision as of 18:03, 30 March 2008
| |||||||
| , resolution 3.00Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | and | ||||||
| Ligands: | , | ||||||
| Activity: | Phosphatidylinositol 3-kinase, with EC number 2.7.1.137 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| 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.
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
Page seeded by OCA on Sun Mar 30 21:03:20 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. | 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
