1he8: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
|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> | |||
}} | }} | ||
| Line 14: | Line 17: | ||
==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. | ||
==About this Structure== | ==About this Structure== | ||
| Line 36: | Line 36: | ||
[[Category: Walker, E H.]] | [[Category: Walker, E H.]] | ||
[[Category: Williams, R L.]] | [[Category: Williams, R L.]] | ||
[[Category: gmppnp]] | [[Category: gmppnp]] | ||
[[Category: gtp]] | [[Category: gtp]] | ||
| Line 52: | Line 50: | ||
[[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'' | ||
