A DFT study of the applicability of the charge balance model in two-metal enzymes: The case of cAMP-dependent protein kinase

We studied the complexes of cAMP-dependent protein kinase with three transition state analogues, namely MgF3−, AlF4− and AlF3. These analogues are meaningfully different among themselves and from the native transition state (PO3−), allowing for the discrimination, in terms of charge and geometry, of what contributes more to the binding energy. We show that PKA prefers to bind AlF4− (same charge, different geometry) over AlF3 (different charge, same geometry), in accordance with experimental data and the charge balance concept. We also detected a correlation between the binding energy and the amount of charge transferred from the TSAs to the enzyme.