Synthesis of hybrid bisnucleoside 5',5"'-P1,P4-tetraphosphates by aminoacyl-tRNA synthetases.

Aminoacyl tRNA synthetases, by means of a back reaction, are able to synthesize certain 5', 5"'-P1, P4-bisnucleoside tetraphosphates of biological importance, such as Ap4A. Here it is shown that HisRS and TrpRS (Bacillus stearothermophilus) and AlaRS (E. coli) also synthesize the hybrid compounds Ap4G, Ap4C, and Ap4U. GlnRS (E. coli) is unable to synthesize any of the above compounds. AlaRS synthesizes Ap4U very poorly, and Ap4C and Ap4G almost as effectively as Ap4A. HisRS and TrpRS synthesize Ap4G, Ap4U and Ap3U quite effectively, and Ap4C very poorly. The fact that hybrid bisnucleoside tetraphosphates can be made by the same enzymes, and at rates comparable to Ap4A, suggests that these compounds may also occur in vivo.