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

FEBS Letters

Lavrik, O.I.¹  Zhukov, Yu.N.²  Biryukov, A.I.²  Khomutov, R.M.² 

[1] Institute of Bioorganic Chemistry, Siberian Branch of the USSR Academy of Sciences, 630090 Novosibirsk, USSR;Engelhardt Institute of Molecular Biology, The USSR Academy of Sciences, 117984 Moscow, USSR

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;   

DOI  :  10.1016/0014-5793(90)81086-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 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.

【 授权许可】

Unknown