Influence of the aminoacyl‐tRNA synthetase inhibitors and the diadenosine‐5'‐tetraphosphate phosphonate analogues on the catalysis of diadenosyl oligophosphates formation

[摘要]

Well-known aminoacyl-tRNA synthetase (ARSase) inhibitors, namely the analogues of amino acids and aminoacyl adenylates (aminoalkyl- and aminophosphonyl adenylates with K _i ⋍ 0.1 μM) as well as the diadenosine 5',5'''-p ¹,p ⁴-tetraphosphate (Ap₄A) phosphonoanalogues, were for the first time used for the Ap₄A biosynthesis regulation. Effects of a set of such compounds on lysyl-, phenylalanyl- and alanyl-tRNA synthetases from E. coli, capable of synthesizing Ap₄A in the presence of Zn²⁺ ions and pyrophosphatase, have been studied. The adenylate analogues were found to inhibit the Ap₄A and Ap₃A formation (I ₅₀ ⋍ 6 mM). Aminophosphonic and aminophosphonous acids are not involved in Ap₃A and Ap₄A biosynthesis and inhibited it at high concentrations. The Ap₄A phosphoanalogues slightly inhibited the major reactions of ARSases, as well as the biosynthesis of Ap₃A and Ap₄A, at a concentration of 5 mM.

[学科分类] 生物化学/生物物理

[关键词] Ap4A synthesis;Aminoacyl-tRNA synthetase;Aminoalkyl adenylate;Aminophosphonyl adenylate;Aminophosphonic acid;Aminophosphonous acid;Ap4A phosphonoanalogue;Ap4A;diadenosine 5';5'''-p 1;p 4-tetraphosphate;Ap3A;diadenosine 5';5'''-p 1;p 3-triphosphate