9HK5
Structure of a mutant of human protein kinase CK2alpha' that equals its isoenzyme CK2alpha in affinity to the regulatory subunit CK2beta
Summary for 9HK5
| Entry DOI | 10.2210/pdb9hk5/pdb |
| Descriptor | Casein kinase II subunit alpha', 1,2-ETHANEDIOL, 5-[(3-chlorophenyl)amino]benzo[c][2,6]naphthyridine-8-carboxylic acid, ... (4 entities in total) |
| Functional Keywords | human protein kinase ck2 human casein kinase 2 isoenzymes ck2alpha and ck2alpha' ck2alpha/ck2beta interaction, transferase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 43381.87 |
| Authors | Werner, C.,Niefind, K. (deposition date: 2024-12-03, release date: 2025-05-07, Last modification date: 2025-07-23) |
| Primary citation | 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., 406:101-115, 2025 Cited by 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: 40223482DOI: 10.1515/hsz-2024-0157 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.491 Å) |
Structure validation
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