Fidelity in the aminoacylation of tRNAVal with hydroxy analogs of valine, leucine, and isoleucine by valyl-tRNA synthetases from Saccharomyces cerevisiae and Escherichia coli

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Abstract
Several analogues of valine, leucine, and isoleucine carrying hydroxyl groups in the .gamma.- or .delta.-position have been tested in the aminoacylation of tRNA by valyl-tRNA synthetases from Saccharamyces cerevisiae and Escherichia coli. Results of the ATP/PPi exchange and of the aminoacylation reactions indicate that the amino acid analogues not only can form the aminoacyl adenylate intermediate but are also transferred to tRNA. However, the fact that the reaction consumes an excess of ATP indicates that the misactivated amino acid analogue is hydrolytically removed. Thus, valyl-tRNA synthetase from S. cerevisiae shows a high fidelity in forming valyl-tRNA. Although the much bulkier amino acid analogues allo- and iso-.gamma.-hydroxyvaline and allo- and iso-.gamma.-hydroxyisoleucine are initially charged to tRNA, the misaminoacylated tRNAVal is enzymatically deacylated. This cleavage reaction is mediated by the hydroxyl groups of the amino acid analogues which are converted into the corresponding lactones.