Inhibition of CK2 Activity by TCDD via Binding to ATP-competitive Binding Site of Catalytic Subunit: Insight from Computational Studies

Alternative mechanisms of toxic effects induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD), instead of the binding to aryl hydrocarbon receptor(AhR), have been taken into consideration. It has been recently shown that TCDD reduces rapidly the activity of CK2(casein kinase II) both in vivo and in vitro. It is found that TCDD has high molecular similarities to the known inhibitors of CK2 catalytic subunit(CK2α). This suggests that TCDD could also be an ATP-competitive inhibitor of CK2α. In this work, docking TCDD to CK2 was carried out based on the two structures of CK2α from maize and human, respectively. The binding free energies of the predicted CK2α-TCDD complexes estimated by the molecular mechanics/Poisson-Boltzmann surface area(MM/PBSA) method are from -85.1 kJ/mol to -114.3 kJ/mol for maize and are from -96.1 kJ/mol to -118.2 kJ/mol for human, which are comparable to those estimated for the known inhibitor and also ATP with CK2α. The energetic analysis also reveals that the van der Waals interaction is the dominant contribution to the binding free energy. These results are also useful for designing new drugs for a target of overexpressing CK2 in cancers.