1gng
From Proteopedia
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[[Image:1gng.gif|left|200px]] | [[Image:1gng.gif|left|200px]] | ||
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'''GLYCOGEN SYNTHASE KINASE-3 BETA (GSK3) COMPLEX WITH FRATTIDE PEPTIDE''' | '''GLYCOGEN SYNTHASE KINASE-3 BETA (GSK3) COMPLEX WITH FRATTIDE PEPTIDE''' | ||
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[[Category: Smith, D G.]] | [[Category: Smith, D G.]] | ||
[[Category: Tanner, R.]] | [[Category: Tanner, R.]] | ||
| - | [[Category: | + | [[Category: Active]] |
| - | [[Category: | + | [[Category: Gsk3/frattide complex]] |
| - | [[Category: | + | [[Category: Phosphorylated]] |
| - | [[Category: | + | [[Category: Protein kinase]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 17:47:00 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 14:47, 2 May 2008
GLYCOGEN SYNTHASE KINASE-3 BETA (GSK3) COMPLEX WITH FRATTIDE PEPTIDE
Overview
BACKGROUND: Glycogen synthase kinase-3 (GSK-3) sequentially phosphorylates four serine residues on glycogen synthase (GS), in the sequence SxxxSxxxSxxx-SxxxS(p), by recognizing and phosphorylating the first serine in the sequence motif SxxxS(P) (where S(p) represents a phosphoserine). FRATtide (a peptide derived from a GSK-3 binding protein) binds to GSK-3 and blocks GSK-3 from interacting with Axin. This inhibits the Axin-dependent phosphorylation of beta-catenin by GSK-3. RESULTS: Structures of uncomplexed Tyr216 phosphorylated GSK-3beta and of its complex with a peptide and a sulfate ion both show the activation loop adopting a conformation similar to that in the phosphorylated and active forms of the related kinases CDK2 and ERK2. The sulfate ion, adjacent to Val214 on the activation loop, represents the binding site for the phosphoserine residue on 'primed' substrates. The peptide FRATtide forms a helix-turn-helix motif in binding to the C-terminal lobe of the kinase domain; the FRATtide binding site is close to, but does not obstruct, the substrate binding channel of GSK-3. FRATtide (and FRAT1) does not inhibit the activity of GSK-3 toward GS. CONCLUSIONS: The Axin binding site on GSK-3 presumably overlaps with that for FRATtide; its proximity to the active site explains how Axin may act as a scaffold protein promoting beta-catenin phosphorylation. Tyrosine 216 phosphorylation can induce an active conformation in the activation loop. Pre-phosphorylated substrate peptides can be modeled into the active site of the enzyme, with the P1 residue occupying a pocket partially formed by phosphotyrosine 216 and the P4 phosphoserine occupying the 'primed' binding site.
About this Structure
1GNG is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The structure of phosphorylated GSK-3beta complexed with a peptide, FRATtide, that inhibits beta-catenin phosphorylation., Bax B, Carter PS, Lewis C, Guy AR, Bridges A, Tanner R, Pettman G, Mannix C, Culbert AA, Brown MJ, Smith DG, Reith AD, Structure. 2001 Dec;9(12):1143-52. PMID:11738041 Page seeded by OCA on Fri May 2 17:47:00 2008
Categories: Homo sapiens | Non-specific serine/threonine protein kinase | Protein complex | Bax, B. | Bridges, A. | Brown, M J.B. | Carter, P. | Culbert, A A. | Guy, A R. | Lewis, C. | Mannix, C. | Pettman, G. | Reith, A D. | Smith, D G. | Tanner, R. | Active | Gsk3/frattide complex | Phosphorylated | Protein kinase
