1o9u
From Proteopedia
| Line 4: | Line 4: | ||
|PDB= 1o9u |SIZE=350|CAPTION= <scene name='initialview01'>1o9u</scene>, resolution 2.40Å | |PDB= 1o9u |SIZE=350|CAPTION= <scene name='initialview01'>1o9u</scene>, resolution 2.40Å | ||
|SITE= <scene name='pdbsite=AC1:Adz+Binding+Site+For+Chain+A'>AC1</scene> | |SITE= <scene name='pdbsite=AC1:Adz+Binding+Site+For+Chain+A'>AC1</scene> | ||
| - | |LIGAND= <scene name='pdbligand=ADZ:9-METHYL-9H-PURIN-6-AMINE'>ADZ</scene> | + | |LIGAND= <scene name='pdbligand=ADZ:9-METHYL-9H-PURIN-6-AMINE'>ADZ</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/ | + | |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= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1o9u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1o9u OCA], [http://www.ebi.ac.uk/pdbsum/1o9u PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1o9u RCSB]</span> | ||
}} | }} | ||
| Line 14: | Line 17: | ||
==Overview== | ==Overview== | ||
Glycogen synthase kinase 3beta (GSK3beta) is a serine/threonine kinase involved in insulin, growth factor and Wnt signalling. In Wnt signalling, GSK3beta is recruited to a multiprotein complex via interaction with axin, where it hyperphosphorylates beta-catenin, marking it for ubiquitylation and destruction. We have now determined the crystal structure of GSK3beta in complex with a minimal GSK3beta-binding segment of axin, at 2.4 A resolution. The structure confirms the co-localization of the binding sites for axin and FRAT in the C-terminal domain of GSK3beta, but reveals significant differences in the interactions made by axin and FRAT, mediated by conformational plasticity of the 285-299 loop in GSK3beta. Detailed comparison of the axin and FRAT GSK3beta complexes allows the generation of highly specific mutations, which abrogate binding of one or the other. Quantitative analysis suggests that the interaction of GSK3beta with the axin scaffold enhances phosphorylation of beta-catenin by >20 000-fold. | Glycogen synthase kinase 3beta (GSK3beta) is a serine/threonine kinase involved in insulin, growth factor and Wnt signalling. In Wnt signalling, GSK3beta is recruited to a multiprotein complex via interaction with axin, where it hyperphosphorylates beta-catenin, marking it for ubiquitylation and destruction. We have now determined the crystal structure of GSK3beta in complex with a minimal GSK3beta-binding segment of axin, at 2.4 A resolution. The structure confirms the co-localization of the binding sites for axin and FRAT in the C-terminal domain of GSK3beta, but reveals significant differences in the interactions made by axin and FRAT, mediated by conformational plasticity of the 285-299 loop in GSK3beta. Detailed comparison of the axin and FRAT GSK3beta complexes allows the generation of highly specific mutations, which abrogate binding of one or the other. Quantitative analysis suggests that the interaction of GSK3beta with the axin scaffold enhances phosphorylation of beta-catenin by >20 000-fold. | ||
| - | |||
| - | ==Disease== | ||
| - | Known diseases associated with this structure: Caudal duplication anomaly OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603816 603816]], Hepatocellular carcinoma, somatic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603816 603816]] | ||
==About this Structure== | ==About this Structure== | ||
| Line 24: | Line 24: | ||
Structural basis for recruitment of glycogen synthase kinase 3beta to the axin-APC scaffold complex., Dajani R, Fraser E, Roe SM, Yeo M, Good VM, Thompson V, Dale TC, Pearl LH, EMBO J. 2003 Feb 3;22(3):494-501. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12554650 12554650] | Structural basis for recruitment of glycogen synthase kinase 3beta to the axin-APC scaffold complex., Dajani R, Fraser E, Roe SM, Yeo M, Good VM, Thompson V, Dale TC, Pearl LH, EMBO J. 2003 Feb 3;22(3):494-501. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12554650 12554650] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| + | [[Category: Non-specific serine/threonine protein kinase]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Transferred entry: 2 7.11 1]] | ||
[[Category: Dajani, R.]] | [[Category: Dajani, R.]] | ||
[[Category: Pearl, L H.]] | [[Category: Pearl, L H.]] | ||
[[Category: Roe, S M.]] | [[Category: Roe, S M.]] | ||
| - | [[Category: | + | [[Category: alternative splicing]] |
[[Category: anti-oncogene]] | [[Category: anti-oncogene]] | ||
[[Category: apoptosis]] | [[Category: apoptosis]] | ||
| + | [[Category: atp-binding]] | ||
[[Category: developmental protein]] | [[Category: developmental protein]] | ||
[[Category: insulin pathway]] | [[Category: insulin pathway]] | ||
| Line 37: | Line 38: | ||
[[Category: multigene family]] | [[Category: multigene family]] | ||
[[Category: phosphorylation]] | [[Category: phosphorylation]] | ||
| - | + | [[Category: serine/threonine -protein kinase]] | |
| - | [[Category: serine/threonine -protein kinase | + | |
[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''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 22:42:02 2008'' |
Revision as of 19:42, 30 March 2008
| |||||||
| , resolution 2.40Å | |||||||
|---|---|---|---|---|---|---|---|
| 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 | ||||||
GLYCOGEN SYNTHASE KINASE 3 BETA COMPLEXED WITH AXIN PEPTIDE
Overview
Glycogen synthase kinase 3beta (GSK3beta) is a serine/threonine kinase involved in insulin, growth factor and Wnt signalling. In Wnt signalling, GSK3beta is recruited to a multiprotein complex via interaction with axin, where it hyperphosphorylates beta-catenin, marking it for ubiquitylation and destruction. We have now determined the crystal structure of GSK3beta in complex with a minimal GSK3beta-binding segment of axin, at 2.4 A resolution. The structure confirms the co-localization of the binding sites for axin and FRAT in the C-terminal domain of GSK3beta, but reveals significant differences in the interactions made by axin and FRAT, mediated by conformational plasticity of the 285-299 loop in GSK3beta. Detailed comparison of the axin and FRAT GSK3beta complexes allows the generation of highly specific mutations, which abrogate binding of one or the other. Quantitative analysis suggests that the interaction of GSK3beta with the axin scaffold enhances phosphorylation of beta-catenin by >20 000-fold.
About this Structure
1O9U is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural basis for recruitment of glycogen synthase kinase 3beta to the axin-APC scaffold complex., Dajani R, Fraser E, Roe SM, Yeo M, Good VM, Thompson V, Dale TC, Pearl LH, EMBO J. 2003 Feb 3;22(3):494-501. PMID:12554650
Page seeded by OCA on Sun Mar 30 22:42:02 2008
Categories: Homo sapiens | Non-specific serine/threonine protein kinase | Protein complex | Dajani, R. | Pearl, L H. | Roe, S M. | Alternative splicing | Anti-oncogene | Apoptosis | Atp-binding | Developmental protein | Insulin pathway | Kinase | Multigene family | Phosphorylation | Serine/threonine -protein kinase | Transferase
