3OFM

Structure of a human CK2alpha prime, the paralog isoform of the catalytic subunit of protein kinase CK2 from Homo sapiens

Summary for 3OFM

• Entry DOI: 10.2210/pdb3ofm/pdb
• Related: 1JWH 3BQC 3E3B
• Descriptor: Casein kinase II subunit alpha', 3-(4,5,6,7-tetrabromo-1H-benzotriazol-1-yl)propan-1-ol, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: eukaryptic protein kinase fold, phospho transferase, atp binding, phosphorylation, cytoplasm and nucleus, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 41789.42

Authors

Bischoff, N.,Olsen, B.,Raaf, J.,Bretner, M.,Issinger, O.-G.,Niefind, K. (deposition date: 2010-08-15, release date: 2011-01-19, Last modification date: 2023-09-06)

Primary citation

Bischoff, N.,Olsen, B.,Raaf, J.,Bretner, M.,Issinger, O.G.,Niefind, K.
Structural basis of the reduced affinity between the protein kinase CK2 subunits CK2alpha prime and CK2beta
J.Mol.Biol., 407:1-12, 2011

PubMed Abstract: Protein kinase CK2 (formerly "casein kinase 2") is composed of a central dimer of noncatalytic subunits (CK2β) binding two catalytic subunits. In humans, there are two isoforms of the catalytic subunit (and an additional splicing variant), one of which (CK2α) is well characterized. To supplement the limited biochemical knowledge about the second paralog (CK2α'), we developed a well-soluble catalytically active full-length mutant of human CK2α', characterized it by Michaelis-Menten kinetics and isothermal titration calorimetry, and determined its crystal structure to a resolution of 2 Å. The affinity of CK2α' for CK2β is about 12 times lower than that of CK2α and is less driven by enthalpy. This result fits the observation that the β4/β5 loop, a key element of the CK2α/CK2β interface, adopts an open conformation in CK2α', while in CK2α, it opens only after assembly with CK2β. The open β4/β5 loop in CK2α' is stabilized by two elements that are absent in CK2α: (1) the extension of the N-terminal β-sheet by an additional β-strand, and (2) the filling of a conserved hydrophobic cavity between the β4/β5 loop and helix αC by a tryptophan residue. Moreover, the interdomain hinge region of CK2α' adopts a fully functional conformation, while unbound CK2α is often found with a nonproductive hinge conformation that is overcome only by CK2β binding. Taken together, CK2α' exhibits a significantly lower affinity for CK2β than CK2α; moreover, in functionally critical regions, it is less dependent on CK2β to obtain a fully functional conformation.

PubMed: 21241709
DOI: 10.1016/j.jmb.2011.01.020

Experimental method

X-RAY DIFFRACTION (2 Å)