1EH4
BINARY COMPLEX OF CASEIN KINASE-1 FROM S. POMBE WITH AN ATP COMPETITIVE INHIBITOR, IC261
Summary for 1EH4
| Entry DOI | 10.2210/pdb1eh4/pdb |
| Related | 1CSN 2CSN |
| Descriptor | CASEIN KINASE-1, SULFATE ION, 3-[(2,4,6-TRIMETHOXY-PHENYL)-METHYLENE]-INDOLIN-2-ONE, ... (4 entities in total) |
| Functional Keywords | protein kinase, casein kinase-1, protein-inhibitor binary complex, transferase |
| Biological source | Schizosaccharomyces pombe (fission yeast) |
| Cellular location | Cytoplasm: P40233 |
| Total number of polymer chains | 2 |
| Total formula weight | 70433.83 |
| Authors | Mashhoon, N.,Demaggio, A.J.,Tereshko, V.,Bergmeier, S.C.,Egli, M.,Hoekstra, M.F.,Kuret, J. (deposition date: 2000-02-18, release date: 2001-09-19, Last modification date: 2024-03-13) |
| Primary citation | Mashhoon, N.,Demaggio, A.J.,Tereshko, V.,Bergmeier, S.C.,Egli, M.,Hoekstra, M.F.,Kuret, J. Crystal Structure of a Conformation-Selective Casein Kinase-1 Inhibitor J.Biol.Chem., 275:20052-20060, 2000 Cited by PubMed Abstract: 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. PubMed: 10749871DOI: 10.1074/jbc.M001713200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
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