2CSN

BINARY COMPLEX OF CASEIN KINASE-1 WITH CKI7

2CSN の概要

• エントリーDOI: 10.2210/pdb2csn/pdb
• 分子名称: CASEIN KINASE-1, SULFATE ION, N-(2-AMINOETHYL)-5-CHLOROISOQUINOLINE-8-SULFONAMIDE, ... (4 entities in total)
• 機能のキーワード: casein kinase-1, protein kinase
• 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: 1
• 化学式量合計: 34723.92

構造登録者

Xu, R.-M.,Cheng, X. (登録日: 1995-10-11, 公開日: 1996-03-08, 最終更新日: 2024-02-14)

主引用文献

Xu, R.M.,Carmel, G.,Kuret, J.,Cheng, X.
Structural basis for selectivity of the isoquinoline sulfonamide family of protein kinase inhibitors.
Proc.Natl.Acad.Sci.USA, 93:6308-6313, 1996

PubMed Abstract: A large family of isoquinoline sulfonamide compounds inhibits protein kinases by competing with adenosine triphosphates(ATP), yet interferes little with the activity of other ATP-using enzymes such as ATPases and adenylate cyclases. One such compound, N-(2-aminoethyl)-5-chloroisoquinoline-8-sulfonamide (CK17), is selective for casein kinase-1 isolated from a variety of sources. Here we report the crystal structure of the catalytic domain of Schizosaccharomyces pombe casein kinase-1 complexed with CK17, refined to a crystallographic R-factor of 17.8% at 2.5 angstrom resolution. The structure provides new insights into the mechanism of the ATP-competing inhibition and the origin of their selectivity toward different protein kinases. Selectivity for protein kinases versus other enzymes is achieved by hydrophobic contacts and the hydrogen bond with isoquinoline ring. We propose that the hydrogen bond involving the ring nitrogen-2 atom of the isoquinoline must be preserved, but that the ring can flip depending on the chemical substituents at ring positions 5 and 8. Selectivity for individual members of the protein kinase family is achieved primarily by interactions with these substituents.

PubMed: 8692811
DOI: 10.1073/pnas.93.13.6308

実験手法

X-RAY DIFFRACTION (2.5 Å)