Misacylation of tRNALys with noncognate amino acids by lysyl-tRNA synthetase.

Abstract

Lysyl-tRNA synthetase (LysRS), a class II enzyme whose major function is to provide Lys-tRNALys for protein synthesis, also catalyzes aminoacylation of tRNALys with arginine, threonine, methionine, leucine, alanine, serine, and cysteine. The limited selectivity in the tRNA aminoacylation reaction appears to be due to inefficient editing of some amino acids (Met, Leu, Cys, Ala, Thr) by a pre-transfer mechanism or the absence of editing of other amino acids (Arg and Ser). Purified Arg-tRNALys, Thr-tRNALys, and Met-tRNALys were essentially not deacylated by LysRS, indicating that the enzyme does not possess a post-transfer editing mechanism. However, LysRS possesses an efficient pre-transfer editing mechanism which prevents misacylation of tRNALys with ornithine. A novel feature of this editing reaction is that ornithine lactam is formed by the facile cyclization of ornithyl adenylate.