9HK5

Structure of a mutant of human protein kinase CK2alpha' that equals its isoenzyme CK2alpha in affinity to the regulatory subunit CK2beta

9HK5 の概要

• エントリーDOI: 10.2210/pdb9hk5/pdb
• 分子名称: Casein kinase II subunit alpha', 1,2-ETHANEDIOL, 5-[(3-chlorophenyl)amino]benzo[c][2,6]naphthyridine-8-carboxylic acid, ... (4 entities in total)
• 機能のキーワード: human protein kinase ck2 human casein kinase 2 isoenzymes ck2alpha and ck2alpha' ck2alpha/ck2beta interaction, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 43381.87

構造登録者

Werner, C.,Niefind, K. (登録日: 2024-12-03, 公開日: 2025-05-07)

主引用文献

Werner, C.,Eimermacher, S.,Harasimowicz, H.,Fischer, D.,Pietsch, M.,Niefind, K.
A CK2 alpha ' mutant indicating why CK2 alpha and CK2 alpha ', the isoforms of the catalytic subunit of human protein kinase CK2, deviate in affinity to CK2 beta.
Biol.Chem., 2025

PubMed Abstract: Protein kinase CK2 (casein kinase 2) mainly exists as heterotetrameric holoenzyme with two catalytic subunits (CK2α or CK2α') bound to a homodimer of non-catalytic subunits (CK2β). With and , the human genome contains two paralogs encoding catalytic CK2 subunits. Both gene products, called CK2α and CK2α', strongly interact with CK2β. An earlier report that CK2α' has a lower CK2β affinity than CK2α is confirmed via isothermal titration calorimetry in this study. Furthermore, we show with a fluorescence-anisotropy assay that a CK2β-competitive peptide binds less strongly to CK2α' than to CK2α. The reason for the reduced affinity of CK2α' to CK2β and CK2β competitors is puzzling: both isoenzymes have identical amino acid compositions at their CK2β interfaces, but the β4β5 loop, a component of this interface, is conformationally less adaptable in CK2α' than in CK2α due to intramolecular constraints. To release these constraints, we constructed a CK2α' mutant that was equalized to CK2α at the backside of the β4β5 loop. Concerning thermostability, affinity to CK2β or CK2β competitors and 3D-structure next to the β4β5 loop, this CK2α' mutant is more similar to CK2α than to its own wild-type, suggesting a critical role of the β4β5 loop adaptability for CK2β affinity.

PubMed: 40223482
DOI: 10.1515/hsz-2024-0157

実験手法

X-RAY DIFFRACTION (1.491 Å)