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Retracing the evolution of amino acid specificity in glutaminyl‐tRNA synthetase
Author(s) -
Hong Kwang-Won,
Ibba Michael,
Söll Dieter
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)00968-5
Subject(s) - transfer rna , biochemistry , chemistry , amino acid , aminoacyl trna synthetase , rna , gene
Molecular phylogenetic studies of glutaminyl‐tRNA synthetase suggest that it has relatively recently evolved from the closely related enzyme glutamyl‐tRNA synthetase. We have now attempted to retrace one of the key steps in this process by selecting glutaminyl‐tRNA synthetase mutants displaying enhanced glutamic acid recognition. Mutagenesis of two residues proximal to the active site, Phe‐90 and Tyr‐240, was found to improve glutamic acid recognition 3–5‐fold in vitro and resulted in the misacylation of tRNA Gln with glutamic acid. In vivo expression of the genes encoding these misacylating variants of glutaminyl‐tRNA synthetase reduced cellular growth rates by 40%, probably as a result of an increase in translational error rates. These results provide the first biochemical evidence that glutaminyl‐tRNA synthetase originated through duplication and consequent diversification of an ancestral glutamyl‐tRNA synthetase‐encoding gene.