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

O.N. Rogacheva, B.F. Shchegolev, E.A. Vershinina, A.A. Tokmakov, V.E. Stefanov

Результат исследований: Научные публикации в периодических изданияхстатья


We used molecular dynamics to find the average path of the A-domain conformational transition in protein kinase A Iα. We obtained thirteen productive trajectories and processed them sequentially using factor and cross-correlation analyses. The conformational transition is presented as partly deterministic sequence of six events. Event B represents transition of the phosphate binding cassette. Main participants of this event form electrostatic switch cAMP(O6)–A202(N-H)–G199(C=O). Through this switch, cAMP transmits information about its binding to hydrophobic switch L203–Y229 and thus triggers conformational transition of A-domain. Events C and D consist in N3A-motif displacement towards phosphate binding cassette and B/C-helix rotation. Event E involves an increase in interaction energy between Y229 and β-subdomain. Taken together, events B, E, and D correspond to the hinge movement towards β-barrel. Transition of B/C-helix turn (a.a. 229–234) from α-form to π-form accounts for event F. Event G implies that π
Язык оригиналаанглийский
ЖурналBioMed Research International
Номер выпуска1-8
СостояниеОпубликовано - 2017