Binding mode prediction of a CK2 inhibitor, Hematein by the MM/PBSA method

Abstract

Casein kinase II (CK2), a serine-threonine protein kinase, is distributed ubiquitously in human body. It exists as a tetramer composed of two catalytic subunits (α and α') and two control subunits (β). Amino acid sequence homology between the catalytic subunit α and α' is very high, 83%. Inhibitors of this enzyme have been explored for cancer, virus infection and glomerulonephritis therapies, and several highly potent compounds have been reported as ATP competitive inhibitors. On the other hand, hematein, a natural compound isolated from Caesalpinia sappan, inhibits CK2α in an ATP uncompetitive manner, whereas it inhibits CK2α' in a competitive manner. We have investigated the binding mode of hematein to both isozymes using docking studies followed by the binding energy analysis with the MM/PBSA method and the simulated annealing simulation. The results suggested that hematein could bind to the ATP binding site of the both isozymes. In addition, it might bind to the allosteric site and the substrate binding site of CK2α.