Biopolym. Cell. 1986; 2(4):179-185.
Structure and Function of Biopolymers
Phosphonate analogs of P1, P4-bis(5'-adenosyl)tetraphosphate (Ap4A) as inhibitors of bovine tryptophanyl-tRNA-synthetase
1Merkulova T. I., 1Nurbekov M. K., 1Tarusova N. B., 1Kovaleva G. K.
  1. Institute of Molecular Biology, Academy of Sciences of the USSR
    Moscow, USSR


Phosphonate analogs of Ap4A—ApcpppA(I), AppcppA(II) and ApcppcpA(III)—inhibit the enzymic activity of bovine tryptophanyl-tRNA-synthetase (EC; I effectively interacts with ATP and PPi binding sites, III — mainly with PPi binding site, and II interacts weakly with both of them. After prolonged incubation (5 h, 37 °C) with I or III an irreversible 80 % inhibition of the enzyme is observed, whereas with II it is only 40 %. The inhibiting action of the Ap4A analogs is shown to be due to the removal of essential Zn2+ ion from the enzyme. Based on these observations, an assumption is made that Zn2+ in the active site of the enzyme is located in or near the PPi binding site.


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