1M2R

Crystal structure of 5,8-di-amino-1,4-di-hydroxy-anthraquinone/CK2 kinase complex

1M2R の概要

• エントリーDOI: 10.2210/pdb1m2r/pdb
• 関連するPDBエントリー: 1F0Q 1J91 1JAM 1M2P 1M2Q
• 分子名称: CASEIN kinase II, alpha chain, 5,8-DI-AMINO-1,4-DIHYDROXY-ANTHRAQUINONE (3 entities in total)
• 機能のキーワード: kinase, inhibitor-enzyme complex, transferase
• 由来する生物種: Zea mays
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 38943.63

構造登録者

De Moliner, E.,Moro, S.,Sarno, S.,Zagotto, G.,Zanotti, G.,Pinna, L.A.,Battistutta, R. (登録日: 2002-06-25, 公開日: 2003-06-17, 最終更新日: 2024-02-14)

主引用文献

De Moliner, E.,Sarno, S.,Moro, S.,Zanotti, G.,Battistutta, R.,Pinna, L.A.
Inhibition of protein kinase CK2 by anthraquinone-related compounds. A structural insight
J.Biol.Chem., 278:1831-1836, 2003

PubMed Abstract: Protein kinases play key roles in signal transduction and therefore are among the most attractive targets for drug design. The pharmacological aptitude of protein kinase inhibitors is highlighted by the observation that various diseases with special reference to cancer are because of the abnormal expression/activity of individual kinases. The resolution of the three-dimensional structure of the target kinase in complex with inhibitors is often the starting point for the rational design of this kind of drugs, some of which are already in advanced clinical trial or even in clinical practice. Here we present and discuss three new crystal structures of ATP site-directed inhibitors in complex with "casein kinase-2" (CK2), a constitutively active protein kinase implicated in a variety of cellular functions and misfunctions. With the help of theoretical calculations, we disclose some key features underlying the inhibitory efficiency of anthraquinone derivatives, outlining three different binding modes into the active site. In particular, we show that a nitro group in a hydroxyanthraquinone scaffold decreases the inhibitory constants K(i) because of electron-withdrawing and resonance effects that enhance the polarization of hydroxylic substituents in paraposition.

PubMed: 12419810
DOI: 10.1074/jbc.M209367200

実験手法

X-RAY DIFFRACTION (1.7 Å)