1q5k: Difference between revisions
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|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=TMU:N-(4-METHOXYBENZYL)-N'-(5-NITRO-1,3-THIAZOL-2-YL)UREA'>TMU</scene> | |LIGAND= <scene name='pdbligand=TMU:N-(4-METHOXYBENZYL)-N'-(5-NITRO-1,3-THIAZOL-2-YL)UREA'>TMU</scene> | ||
|ACTIVITY= [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] | |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= GSK3B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= GSK3B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1q5k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q5k OCA], [http://www.ebi.ac.uk/pdbsum/1q5k PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1q5k RCSB]</span> | |||
}} | }} | ||
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[[Category: Radesater, A C.]] | [[Category: Radesater, A C.]] | ||
[[Category: Xue, Y.]] | [[Category: Xue, Y.]] | ||
[[Category: kinase-inhibitor complex]] | [[Category: kinase-inhibitor complex]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 23 | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:09:09 2008'' | ||
Revision as of 20:09, 30 March 2008
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| 1q5k, resolution 1.94Å | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Ligands: | TMU | ||||||||||||
| Gene: | GSK3B (Homo sapiens) | ||||||||||||
| 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 | ||||||||||||
crystal structure of Glycogen synthase kinase 3 in complexed with inhibitor
Overview
Glycogen synthase kinase 3 (GSK3) is a serine/threonine kinase that has been implicated in pathological conditions such as diabetes and Alzheimer's disease. We report the characterization of a GSK3 inhibitor, AR-A014418, which inhibits GSK3 (IC50 = 104 +/- 27 nM), in an ATP-competitive manner (Ki = 38 nM). AR-A014418 does not significantly inhibit cdk2 or cdk5 (IC50 > 100 microM) or 26 other kinases demonstrating high specificity for GSK3. We report the co-crystallization of AR-A014418 with the GSK3beta protein and provide a description of the interactions within the ATP pocket, as well as an understanding of the structural basis for the selectivity of AR-A014418. AR-A014418 inhibits tau phosphorylation at a GSK3-specific site (Ser-396) in cells stably expressing human four-repeat tau protein. AR-A014418 protects N2A neuroblastoma cells against cell death mediated by inhibition of the phosphatidylinositol 3-kinase/protein kinase B survival pathway. Furthermore, AR-A014418 inhibits neurodegeneration mediated by beta-amyloid peptide in hippocampal slices. AR-A014418 may thus have important applications as a tool to elucidate the role of GSK3 in cellular signaling and possibly in Alzheimer's disease. AR-A014418 is the first compound of a family of specific inhibitors of GSK3 that does not significantly inhibit closely related kinases such as cdk2 or cdk5.
About this Structure
1Q5K is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural insights and biological effects of glycogen synthase kinase 3-specific inhibitor AR-A014418., Bhat R, Xue Y, Berg S, Hellberg S, Ormo M, Nilsson Y, Radesater AC, Jerning E, Markgren PO, Borgegard T, Nylof M, Gimenez-Cassina A, Hernandez F, Lucas JJ, Diaz-Nido J, Avila J, J Biol Chem. 2003 Nov 14;278(46):45937-45. Epub 2003 Aug 19. PMID:12928438
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Proteopedia Page Contributors and Editors (what is this?)
- Pages with broken file links
- Homo sapiens
- Non-specific serine/threonine protein kinase
- Single protein
- Avila, J.
- Berg, S.
- Bhat, R.
- Borgegard, T.
- Diaz-Mido, J.
- Gimenez-Cassina, A.
- Hellberg, S.
- Hernandez, F.
- Jerning, E.
- Lucas, J J.
- Markgren, P O.
- Nilsson, Y.
- Nylof, M.
- Ormo, M.
- Radesater, A C.
- Xue, Y.
- Kinase-inhibitor complex
