Paper Citing NAMD - Abstract
Rogacheva, O.N.; Shchegolev, B.F.; Stefanov, V.E.; Zakharov, G.A.; SavvateevaPopova, E.V.
A202 AND A326 ARE CRITICAL RESIDUES FOR INITIATION OF 3':5'-AMP-INDUCED PROTEIN KINASE A Ialpha REGULATORY SUBUNIT CONFORMATIONAL TRANSITION. Part I
BIOCHEMISTRY (MOSCOW), 77:568-577, 2012
Using protein-ligand docking and molecular dynamics, we demonstrated that the key event initiated by 3':5'-AMP binding to A- and B domains of Protein Kinase A Ialpha regulatory subunit is hydrogen bond formation between 3':5'- AMP and A202(A326). The A202(A326) amide group movement associated with the bond formation leads to the reorganization of the Phosphate Binding Cassette (short 310-helix becomes long alpha-helix). This process results in L203(L327) displacement and finally causes hinge (B-helix) rotation. L203(L327) displacement and its packing into a hydrophobic pocket that is formed by Phosphate Binding Cassette and beta2beta3-loop also depends on the beta2beta3-loop conformation. The correct conformation is maintained by R, I, E, but not K in 209(333) position of the A- and B- domains. So, R209K and R333K mutants meet difficulties in reaching B conformation. The apo form of 3':5'-AMP- binding domain also undergoes the transition from H- to B-conformation. In this case the A202(A326) amide group movement appears to have resulted from the reorganization of the Phosphate Binding Cassette into more stable alpha- helix.
