1eh4: Difference between revisions
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'''BINARY COMPLEX OF CASEIN KINASE-1 FROM S. POMBE WITH AN ATP COMPETITIVE INHIBITOR, IC261''' | {{Structure | ||
|PDB= 1eh4 |SIZE=350|CAPTION= <scene name='initialview01'>1eh4</scene>, resolution 2.80Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=IC1:3-[(2,4,6-TRIMETHOXY-PHENYL)-METHYLENE]-INDOLIN-2-ONE'>IC1</scene> | |||
|ACTIVITY= | |||
|GENE= | |||
}} | |||
'''BINARY COMPLEX OF CASEIN KINASE-1 FROM S. POMBE WITH AN ATP COMPETITIVE INHIBITOR, IC261''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1EH4 is a [ | 1EH4 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Schizosaccharomyces_pombe Schizosaccharomyces pombe]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EH4 OCA]. | ||
==Reference== | ==Reference== | ||
Crystal structure of a conformation-selective casein kinase-1 inhibitor., Mashhoon N, DeMaggio AJ, Tereshko V, Bergmeier SC, Egli M, Hoekstra MF, Kuret J, J Biol Chem. 2000 Jun 30;275(26):20052-60. PMID:[http:// | Crystal structure of a conformation-selective casein kinase-1 inhibitor., Mashhoon N, DeMaggio AJ, Tereshko V, Bergmeier SC, Egli M, Hoekstra MF, Kuret J, J Biol Chem. 2000 Jun 30;275(26):20052-60. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10749871 10749871] | ||
[[Category: Schizosaccharomyces pombe]] | [[Category: Schizosaccharomyces pombe]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: protein-inhibitor binary complex]] | [[Category: protein-inhibitor binary complex]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:55:38 2008'' | ||
Revision as of 08:55, 20 March 2008
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| 1eh4, resolution 2.80Å | |||||||||||||
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| Ligands: | SO4 and IC1 | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
BINARY COMPLEX OF CASEIN KINASE-1 FROM S. POMBE WITH AN ATP COMPETITIVE INHIBITOR, IC261
Overview
Members of the casein kinase-1 family of protein kinases play an essential role in cell regulation and disease pathogenesis. Unlike most protein kinases, they appear to function as constitutively active enzymes. As a result, selective pharmacological inhibitors can play an important role in dissection of casein kinase-1-dependent processes. To address this need, new small molecule inhibitors of casein kinase-1 acting through ATP-competitive and ATP-noncompetitive mechanisms were isolated on the basis of in vitro screening. Here we report the crystal structure of 3-[(2,4,6-trimethoxyphenyl) methylidenyl]-indolin-2-one (IC261), an ATP-competitive inhibitor with differential activity among casein kinase-1 isoforms, in complex with the catalytic domain of fission yeast casein kinase-1 refined to a crystallographic R-factor of 22.4% at 2.8 A resolution. The structure reveals that IC261 stabilizes casein kinase-1 in a conformation midway between nucleotide substrate liganded and nonliganded conformations. We propose that adoption of this conformation by casein kinase-1 family members stabilizes a delocalized network of side chain interactions and results in a decreased dissociation rate of inhibitor.
About this Structure
1EH4 is a Single protein structure of sequence from Schizosaccharomyces pombe. Full crystallographic information is available from OCA.
Reference
Crystal structure of a conformation-selective casein kinase-1 inhibitor., Mashhoon N, DeMaggio AJ, Tereshko V, Bergmeier SC, Egli M, Hoekstra MF, Kuret J, J Biol Chem. 2000 Jun 30;275(26):20052-60. PMID:10749871
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