Abstract
Protein-ligand docking and molecular dynamics studies have shown that the key event initiated by 3′:5′-AMP binding to the A- and B-domains of protein kinase A Iα regulatory subunit is formation of a hydrogen bond between 3′:5′-AMP and A202(A326) (the residue in parentheses being from the B-domain). The A202(A326) amide group movement associated with the bond formation leads to reorganization of the phosphate binding cassette (PBC) (the short 310-helix becomes the long α-helix). This process results in L203(L327) displacement and finally causes hinge (B-helix) rotation. The L203(L327) displacement and packing into the hydrophobic pocket formed by the PBC and β2β3-loop also depends on the β2β3-loop conformation. The correct conformation is maintained by R, I, E, but not K at position 209(333) of the A- and B-domains. So, the R209K and R333K mutants have problems with reaching B-conformation. The apo-form of the 3′:5′-AMP-binding domain also undergoes transition from H- to B-conformation. In this case, the movement of A202(A326) amide group seems to be a result of reorganization of the PBC into a more stable α-helix.
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Abbreviations
- 3′:5′-AMP:
-
cyclic adenosine-3′,5′-monophosphate
- C-subunit:
-
catalytic subunit
- PBC:
-
phosphate binding cassette
- PKA Iα:
-
protein kinase A Iα
- R-subunit:
-
regulatory subunit
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Original Russian Text © O. N. Rogacheva, B. F. Shchegolev, V. E. Stefanov, G. A. Zakharov, E. V. Savvateeva-Popova, 2012, published in Biokhimiya, 2012, Vol. 77, No. 5, pp. 568–577.
Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM12-010, March 18, 2012.
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Rogacheva, O.N., Shchegolev, B.F., Stefanov, V.E. et al. Initiation of the 3′:5′-AMP-induced protein kinase A Iα regulatory subunit conformational transition. Part I. A202 and A326 are critical residues. Biochemistry Moscow 77, 456–464 (2012). https://doi.org/10.1134/S0006297912050057
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DOI: https://doi.org/10.1134/S0006297912050057