1h10: Difference between revisions
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[[Image:1h10.gif|left|200px]] | [[Image:1h10.gif|left|200px]] | ||
'''HIGH RESOLUTION STRUCTURE OF THE PLECKSTRIN HOMOLOGY DOMAIN OF PROTEIN KINASE B/AKT BOUND TO INS(1,3,4,5)-TETRAKISPHOPHATE''' | {{Structure | ||
|PDB= 1h10 |SIZE=350|CAPTION= <scene name='initialview01'>1h10</scene>, resolution 1.40Å | |||
|SITE= <scene name='pdbsite=1:Its+Binding+Site+For+Chain+A'>1</scene> | |||
|LIGAND= <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene> and <scene name='pdbligand=4IP:INOSITOL-(1,3,4,5)-TETRAKISPHOSPHATE'>4IP</scene> | |||
|ACTIVITY= | |||
|GENE= | |||
}} | |||
'''HIGH RESOLUTION STRUCTURE OF THE PLECKSTRIN HOMOLOGY DOMAIN OF PROTEIN KINASE B/AKT BOUND TO INS(1,3,4,5)-TETRAKISPHOPHATE''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1H10 is a [ | 1H10 is a [[Single protein]] structure of sequence 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=1H10 OCA]. | ||
==Reference== | ==Reference== | ||
High-resolution structure of the pleckstrin homology domain of protein kinase b/akt bound to phosphatidylinositol (3,4,5)-trisphosphate., Thomas CC, Deak M, Alessi DR, van Aalten DM, Curr Biol. 2002 Jul 23;12(14):1256-62. PMID:[http:// | High-resolution structure of the pleckstrin homology domain of protein kinase b/akt bound to phosphatidylinositol (3,4,5)-trisphosphate., Thomas CC, Deak M, Alessi DR, van Aalten DM, Curr Biol. 2002 Jul 23;12(14):1256-62. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12176338 12176338] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: ACE]] | [[Category: ACE]] | ||
[[Category: inositol tetrakisphophate]] | [[Category: inositol tetrakisphophate]] | ||
[[Category: | [[Category: phosphoinositide]] | ||
[[Category: phosphorylation]] | [[Category: phosphorylation]] | ||
[[Category: pleckstrin]] | [[Category: pleckstrin]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:30:40 2008'' | ||
Revision as of 12:30, 20 March 2008
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| Coordinates: | save as pdb, mmCIF, xml | ||||||
HIGH RESOLUTION STRUCTURE OF THE PLECKSTRIN HOMOLOGY DOMAIN OF PROTEIN KINASE B/AKT BOUND TO INS(1,3,4,5)-TETRAKISPHOPHATE
OverviewOverview
The products of PI 3-kinase activation, PtdIns(3,4,5)P3 and its immediate breakdown product PtdIns(3,4)P2, trigger physiological processes, by interacting with proteins possessing pleckstrin homology (PH) domains. One of the best characterized PtdIns(3,4,5)P3/PtdIns(3,4)P2 effector proteins is protein kinase B (PKB), also known as Akt. PKB possesses a PH domain located at its N terminus, and this domain binds specifically to PtdIns(3,4,5)P3 and PtdIns(3,4)P2 with similar affinity. Following activation of PI 3-kinase, PKB is recruited to the plasma membrane by virtue of its interaction with PtdIns(3,4,5)P3/PtdIns(3,4)P2. PKB is then activated by the 3-phosphoinositide-dependent pro-tein kinase-1 (PDK1), which like PKB, possesses a PtdIns(3,4,5)P3/PtdIns(3,4)P2 binding PH domain. Here, we describe the high-resolution crystal structure of the isolated PH domain of PKB(alpha) in complex with the head group of PtdIns(3,4,5)P3. The head group has a significantly different orientation and location compared to other Ins(1,3,4,5)P4 binding PH domains. Mutagenesis of the basic residues that form ionic interactions with the D3 and D4 phosphate groups reduces or abolishes the ability of PKB to interact with PtdIns(3,4,5)P3 and PtdIns(3,4)P2. The D5 phosphate faces the solvent and forms no significant interactions with any residue on the PH domain, and this explains why PKB interacts with similar affinity with both PtdIns(3,4,5)P3 and PtdIns(3,4)P2.
DiseaseDisease
Known diseases associated with this structure: Breast cancer, somatic OMIM:[164730], Colorectal cancer, somatic OMIM:[164730], Neutrophil immunodeficiency syndrome OMIM:[602049], Ovarian cancer, somatic OMIM:[164730], Schizophrenia, susceptibility to OMIM:[164730]
About this StructureAbout this Structure
1H10 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
High-resolution structure of the pleckstrin homology domain of protein kinase b/akt bound to phosphatidylinositol (3,4,5)-trisphosphate., Thomas CC, Deak M, Alessi DR, van Aalten DM, Curr Biol. 2002 Jul 23;12(14):1256-62. PMID:12176338
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