Abstract
CK2 is a pleiotropic, constitutively active protein kinase responsible for the phosphorylation of more than 300 physiological substrates. Typically, this enzyme is found in tetrameric form consisting of two regulatory subunits CK2β and two catalytic subunits CK2α or CK2α′. Several natural occurring flavonoids were tested for their ability to inhibit both CK2 holoenzymes, CK2α2β2 and CK2α′2β2. We identified few substances selectively inhibiting only the α′ subunit. Other compounds showed similar effect towards all four isoforms. In some cases, like chrysoeriol, pedalitin, apigenin, and luteolin, the α2β2 holoenzyme was at least six times better inhibited than the free α subunit. Otherwise, we have found a luteolin derivative decreased the kinase activity of CK2α′ with an IC50 value of 0.8 μM, but the holoenzyme only with 9.5 µM.
Highlights
Protein kinase CK2 is a highly conserved serine/threonine kinase considered as constitutively active and ubiquitously expressed
The tetrameric isoforms consist of two catalytic subunits each bound to a regulatory subunit CK2β whereas two of them form a dimer
We had described the inhibitory effect of different substances like halogenated 1H-benzimidazoles and flavonoid compounds towards human catalytic subunits CK2α and CK2α′ [20, 23]
Summary
Protein kinase CK2 is a highly conserved serine/threonine kinase considered as constitutively active and ubiquitously expressed. CK2 can function as monomeric kinases, and as tetrameric complexes. The monomeric forms are designated as CK2α and CK2α′, being the catalytic subunits of CK2. The tetrameric isoforms consist of two catalytic subunits each bound to a regulatory subunit CK2β whereas two of them form a dimer. Within the CK2 holoenzyme, Both catalytic subunits possess very similar N-terminal amino acid sequences, whereas they differ at the C-terminal part. Characteristic features are the ATP-binding motif (G46XGXXS51), the catalytic loop (residues R155, D156 and H160), the activation loop (sequences D175WG177 and G199PE201), and the substrate binding site (residues R 191, R195, K198, and K74-R80) [14, 15]
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