Quantum chemical study on the catalytic mechanism of the C-subunit of cAMP-dependent protein kinase

Quantum chemical calculations were performed to clarify the catalytic mechanism of the catalytic subunit (C-subunit) of cAMP-dependent protein kinase (cAPK). The Schrodinger equation for the model reaction system was solved using the density functional theory (I)FT). A Mg2+ ion resides at the active site and maintains a six-coordinated structure with a ternary complex, which consists of a C-subunit, Mg2+-ATP, and a substrate (protein kinases). It was found that the phosphorylation of the substrate (protein kinases) by the C-subunit of cAPK was a one-step reaction and that the phosphorylated substrate was spontaneously released from the C-subunit. The activation energy required for this phosphorylation was estimated to be 36.23 kcal/mol. Hence, this reaction is expected to proceed at a body temperature of about 310 K. The final product was more stable than the initial reactant, and the energy difference between them was mol.