TRNA enzyme variations

Variations in the level of aminoacylation of tRNA arising from the altered specificity of an aminoacyl-tRNA synthetase or from an amino acid depletion would be expected to exert a profound effect on the rate and level of protein synthesis. There are reports that qualitative changes in aminoacyl-tRNA synthetases may occur during embryo development [58] and in different tissues and organs [15] and that multiple synthetases may occur [59]. However, with the knowledge that mitochondria contain unique synthetases, a reexamination of these data in terms of the localization of the enzymes would help in clarification. 

Another enzyme whose function is of central importance to histidine assimilation is the histidyl-tRNA synthetase. The quantity of this enzyme in the cell does not vary with the availability of histidine [19]. However, the activity of the enzyme probably is sensitive to cellular conditions. Studies of the purified synthetase have established the values of its substrates to be 140 nM for ATP, 26 nM for histidine, and 0.04 nM for tRNA" [20,21]. The intracellular concentration of histidine [18] is very close to its K value, so variations in its concentration should readily influence the activity of the synthetase. 

Enzyme-tRNA cocrystal structures have also provided clues to the catalytic mechanisms used by AARSs. In the case of the Class I glutaminyl-tRNA synthetase (GlnRS) complexed with its cognate tRNA ", the structure of the complex identified variations in the tRNA architecture compared with uncomplexed tRNA. GlnRS makes essential contacts with nucieotides in the tRNA " anticodon, and in the cocrystal structure these nucleotides were indeed splayed out from their normal positions to interact closely with amino acids of the enzyme. Furthermore, the acceptor end of the tRNA showed significant distortion compared to the expected helical structure. The first base pair of the acceptor helix was broken, and the 3 -end of the tRNA bent back in a hairpin conformation toward the rest of the helix (Fig. 3). Such a folded-back orientation of the acceptor end of tRNA " is necessary for the 3 -terminus to reach the glutaminyl adenylate in the enzyme active site. Furthermore, amino acid residues in the enzyme s active... 

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