The replacement of ATP by the competitive inhibitor emodin induces conformational modifications in the catalytic site of protein kinase CK2.

The structure of a complex between the catalytic subunit of Zea mays CK2 and the nucleotide binding site-directed inhibitor emodin (3-methyl-1,6,8-trihydroxyanthraquinone) was solved at 2.6-A resolution. Emodin enters the nucleotide binding site of the enzyme, filling a hydrophobic pocket between the N-terminal and the C-terminal lobes, in the proximity of the site occupied by the base rings of the natural co-substrates. The interactions between the inhibitor and CK2 alpha are mainly hydrophobic. Although the C-terminal domain of the enzyme is essentially identical to the ATP-bound form, the beta-sheet in the N-terminal domain is altered by the presence of emodin. The structural data presented here highlight the flexibility of the kinase domain structure and provide information for the design of selective ATP competitive inhibitors of protein kinase CK2.