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1o6k

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|PDB= 1o6k |SIZE=350|CAPTION= <scene name='initialview01'>1o6k</scene>, resolution 1.70&Aring;
|PDB= 1o6k |SIZE=350|CAPTION= <scene name='initialview01'>1o6k</scene>, resolution 1.70&Aring;
|SITE= <scene name='pdbsite=AC1:Mn+Binding+Site+For+Chain+A'>AC1</scene>
|SITE= <scene name='pdbsite=AC1:Mn+Binding+Site+For+Chain+A'>AC1</scene>
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|LIGAND= <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene> and <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER'>ANP</scene>
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|LIGAND= <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene>
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|ACTIVITY= [http://en.wikipedia.org/wiki/Transferred_entry:_2.7.11.1 Transferred entry: 2.7.11.1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.37 2.7.1.37]
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span>
|GENE=
|GENE=
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|DOMAIN=
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1o6k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1o6k OCA], [http://www.ebi.ac.uk/pdbsum/1o6k PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1o6k RCSB]</span>
}}
}}
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==Overview==
==Overview==
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.
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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==Disease==
 
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Known disease associated with this structure: Diabetes mellitus, type II OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164731 164731]]
 
==About this Structure==
==About this Structure==
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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:[http://www.ncbi.nlm.nih.gov/pubmed/12434148 12434148]
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:[http://www.ncbi.nlm.nih.gov/pubmed/12434148 12434148]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Protein complex]]
[[Category: Protein complex]]
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[[Category: Transferred entry: 2 7.11 1]]
 
[[Category: Barford, D.]]
[[Category: Barford, D.]]
[[Category: Cron, P.]]
[[Category: Cron, P.]]
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[[Category: Thompson, V.]]
[[Category: Thompson, V.]]
[[Category: Yang, J.]]
[[Category: Yang, J.]]
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[[Category: ANP]]
 
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[[Category: MN]]
 
[[Category: protein kinase]]
[[Category: protein kinase]]
[[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 Thu Mar 20 13:06:26 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:40:34 2008''

Revision as of 19:40, 30 March 2008

Image:1o6k.gif


PDB ID 1o6k

Drag the structure with the mouse to rotate
, resolution 1.70Å
Sites:
Ligands: , ,
Activity: Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



STRUCTURE OF ACTIVATED FORM OF PKB KINASE DOMAIN S474D WITH GSK3 PEPTIDE AND AMP-PNP


Overview

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.

About this Structure

1O6K 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

Page seeded by OCA on Sun Mar 30 22:40:34 2008

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