1eh4
From Proteopedia
OCA (Talk | contribs)
(New page: 200px<br /><applet load="1eh4" size="450" color="white" frame="true" align="right" spinBox="true" caption="1eh4, resolution 2.80Å" /> '''BINARY COMPLEX OF CA...)
Next diff →
Revision as of 11:52, 20 November 2007
|
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 with SO4 and IC1 as ligands. 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
Page seeded by OCA on Tue Nov 20 14:00:07 2007
