Initiation of the 3':5'-AMP-induced protein kinase A Iα regulatory subunit conformational transition. Part II. Inhibition by Rp-3':5'-AMPS.
Protein-ligand docking and ab initio calculations have shown that the 3':5'-AMP phosphorothioate analog (Rp-3':5'-AMPS) blocks the A326 amide group displacement typical of transition from the H- to B-conformation within the B-domain of protein kinase A Iα R-subunit. This behavior of Rp-3':5'-AMPS leads to the inhibition of initial stages of hydrophobic relay operation. In accordance with the proposed hypothesis, Rp-3':5'-AMPS similarly to 3':5'-AMP forms a hydrogen bond with the amide group of A326; however, the properties of this bond together with the position of the sulfur atom prevent the movement of A326. Finally, the Rp-3':5'-AMPS-bound domain appears to be locked in the H-conformation, which is in agreement with the X-ray data.
St. Petersburg State University, Universitetskaya nab. 7/9, 199034 St. Petersburg, Russia. AcerLaetum@yandex.ru
O N
ON
Rogacheva
B F
BF
Shchegolev
V E
VE
Stefanov
E V
EV
Savvateeva-Popova
D001665:Binding Sites; D003198:Computer Simulation; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000378:metabolism; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / Q000737:chemistry* / Q000378:metabolism; D006860:Hydrogen Bonding; D017434:Protein Structure, Tertiary; D011789:Quantum Theory
D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D000242:Cyclic AMP