1EH4

BINARY COMPLEX OF CASEIN KINASE-1 FROM S. POMBE WITH AN ATP COMPETITIVE INHIBITOR, IC261

1EH4 の概要

• エントリーDOI: 10.2210/pdb1eh4/pdb
• 関連するPDBエントリー: 1CSN 2CSN
• 分子名称: CASEIN KINASE-1, SULFATE ION, 3-[(2,4,6-TRIMETHOXY-PHENYL)-METHYLENE]-INDOLIN-2-ONE, ... (4 entities in total)
• 機能のキーワード: protein kinase, casein kinase-1, protein-inhibitor binary complex, transferase
• 由来する生物種: Schizosaccharomyces pombe (fission yeast)
• 細胞内の位置: Cytoplasm: P40233
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 70433.83

構造登録者

Mashhoon, N.,Demaggio, A.J.,Tereshko, V.,Bergmeier, S.C.,Egli, M.,Hoekstra, M.F.,Kuret, J. (登録日: 2000-02-18, 公開日: 2001-09-19, 最終更新日: 2024-03-13)

主引用文献

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

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: 10749871
DOI: 10.1074/jbc.M001713200

実験手法

X-RAY DIFFRACTION (2.8 Å)