Role of arginine 209 in the conformational transition of the protein kinase A regulatory subunit RIα A-domain.
Using the combination of molecular dynamics (MD) simulations and geometric clustering we analyzed the role of arginine at 209 position in the transition of protein kinase A Iα (PKA Iα) regulatory subunit A-domain from H- to B-conformation and stabilization of the latter. The mechanism underlying the role of the residue at position 209 in the realization of B-conformation includes: (1) possibility to bind the ligand tightly (if transition happens in the presence of cAMP), (2) capability to hold β2β3-loop in the correct conformation, (3) tendency of residue at 209 position to stabilize B-conformation in the absence and in presence of the ligand. In terms of the effect produced on transition of A-domain from H- to B-conformation in the presence of cAMP, mutational substitutions for R209 can be arranged in the following order: Glu(Gly)>Lys>Ile. In the absence of cAMP the order is different Lys>Gly>Glu>Ile. Thus, our results allow us to presume that the role of arginine at 209 position can be important though not crucial.
St. Petersburg State University, Universitetskaya nab. 7/9, 199034 St. Petersburg, Russia.
Olga N
ON
Rogacheva
Vasiliy E
VE
Stefanov
Boris F
BF
Shchegolev
Elena A
EA
Vershinina
Elena V
EV
Savvateeva-Popova
D001120:Arginine / Q000737:chemistry*; D001665:Binding Sites; D003198:Computer Simulation; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / Q000737:chemistry* / Q000648:ultrastructure*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry* / Q000648:ultrastructure*; D008956:Models, Chemical; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D021122:Protein Subunits
D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D021122:Protein Subunits; D001120:Arginine; D017868:Cyclic AMP-Dependent Protein Kinases