1o6l

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[[Image:1o6l.gif|left|200px]]
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{{Seed}}
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{{STRUCTURE_1o6l| PDB=1o6l | SCENE= }}
{{STRUCTURE_1o6l| PDB=1o6l | SCENE= }}
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'''CRYSTAL STRUCTURE OF AN ACTIVATED AKT/PROTEIN KINASE B (PKB-PIF CHIMERA) TERNARY COMPLEX WITH AMP-PNP AND GSK3 PEPTIDE'''
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===CRYSTAL STRUCTURE OF AN ACTIVATED AKT/PROTEIN KINASE B (PKB-PIF CHIMERA) TERNARY COMPLEX WITH AMP-PNP AND GSK3 PEPTIDE===
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==Overview==
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The protein kinase Akt/PKB is stimulated by the phosphorylation of two regulatory residues, Thr 309 of the activation segment and Ser 474 of the hydrophobic motif (HM), that are structurally and functionally conserved within the AGC kinase family. To understand the mechanism of PKB regulation, we determined the crystal structures of activated kinase domains of PKB in complex with a GSK3beta-peptide substrate and an ATP analog. The activated state of the kinase was generated by phosphorylating Thr 309 using PDK1 and mimicking Ser 474 phosphorylation either with the S474D substitution or by replacing the HM of PKB with that of PIFtide, a potent mimic of a phosphorylated HM. Comparison with the inactive PKB structure indicates that the role of Ser 474 phosphorylation is to promote the engagement of the HM with the N-lobe of the kinase domain, promoting a disorder-to-order transition of the alphaC helix. The alphaC helix, by interacting with pThr 309, restructures and orders the activation segment, generating an active kinase conformation. Analysis of the interactions between PKB and the GSK3beta-peptide explains how PKB selects for protein substrates distinct from those of PKA.
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The line below this paragraph, {{ABSTRACT_PUBMED_12434148}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 12434148 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12434148}}
==About this Structure==
==About this Structure==
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[[Category: Serine/threonine-protein kinase]]
[[Category: Serine/threonine-protein kinase]]
[[Category: Transferase]]
[[Category: Transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 03:26:50 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 14:07:20 2008''

Revision as of 11:07, 27 July 2008

Image:1o6l.png

Template:STRUCTURE 1o6l

CRYSTAL STRUCTURE OF AN ACTIVATED AKT/PROTEIN KINASE B (PKB-PIF CHIMERA) TERNARY COMPLEX WITH AMP-PNP AND GSK3 PEPTIDE

Template:ABSTRACT PUBMED 12434148

About this Structure

1O6L is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Crystal structure of an activated Akt/protein kinase B ternary complex with GSK3-peptide and AMP-PNP., Yang J, Cron P, Good VM, Thompson V, Hemmings BA, Barford D, Nat Struct Biol. 2002 Dec;9(12):940-4. PMID:12434148

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