Electrostatic Switch Function in the Mechanism of Protein Kinase A I Activation: Results of the Molecular Dynamics Simulation

Figure 1

A-domain conformational transition, event B. (a) Before event B (H-conformation). (b) After event B. Colored beads show key atoms of the cAMP(O6)–A202(N-H)–G199(C=O) electrostatic relay: exocyclic oxygen O6 and amide nitrogen of A202 are shown with beads, with black line denoting distance between these atoms equal to 5.2 and 3.4 Ǻ in H-conformation and B-conformation, respectively. In (a), L203 side chain is directed away from the hydrophobic pocket formed by β2β3-loop. In (b), L203 is packed into the hydrophobic pocket. Here and elsewhere, colored ribbons show elements of the secondary structure: rose, N3A-motif; dark yellow, PBC; violet, β2β3-loop; purple, B/C- or B- and C-helices; separately highlighted are critical residues and cAMP.

(a)

(b)