4IB5

Structure of human protein kinase CK2 catalytic subunit in complex with a CK2beta-competitive cyclic peptide

4IB5 の概要

• エントリーDOI: 10.2210/pdb4ib5/pdb
• 関連するPDBエントリー: 1jwh 1PJK 2PVR
• 分子名称: Casein kinase II subunit alpha, CK2beta-derived cyclic peptide, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: protein kinase fold, protein phosphorylation, binding of ck2beta, phosphorylation, nucleus, transferase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 126790.20

構造登録者

Raaf, J.,Guerra, B.,Neundorf, I.,Bopp, B.,Issinger, O.-G.,Jose, J.,Pietsch, M.,Niefind, K. (登録日: 2012-12-08, 公開日: 2013-03-20, 最終更新日: 2024-10-30)

主引用文献

Raaf, J.,Guerra, B.,Neundorf, I.,Bopp, B.,Issinger, O.G.,Jose, J.,Pietsch, M.,Niefind, K.
First structure of protein kinase CK2 catalytic subunit with an effective CK2 beta-competitive ligand
Acs Chem.Biol., 8:901-907, 2013

PubMed Abstract: The constitutively active Ser/Thr kinase CK2 (casein kinase 2) is used by tumor cells to acquire apoptosis resistance. CK2 exists as a heterotetrameric holoenzyme with two catalytic chains (CK2α) attached to a dimer of noncatalytic subunits (CK2β). A druggable cavity at the CK2β interface of CK2α allows the design of small molecules disturbing the CK2α/CK2β interaction and thus affecting activity, stability, and substrate specificity. We describe here the first structure of CK2α with an effective CK2β-competitive compound, namely, a 13-meric cyclic peptide derived from the C-terminal CK2β segment. Some well-ordered water molecules not visible in CK2 holoenzyme structures were detected at the interface. Driven mainly by enthalpy, the peptide binds with submicromolar affinity to CK2α, stimulates its catalytic activity, and reduces effectively the CK2α/CK2β affinity. The results provide a thermodynamic and structural rationalization of the peptide's CK2β-competitive functionality and pave thus the way to a peptidomimetic drug addressing the CK2α/CK2β interaction.

PubMed: 23474121
DOI: 10.1021/cb3007133

実験手法

X-RAY DIFFRACTION (2.2 Å)