GLUTAMYL-TRANSFER-RNA SYNTHETASE

Glutamyl-tRNA synthetase (GluRS) belongs to the class I aminoacyl-tRNA synthetases and shows several similarities with glutaminyl-tRNA synth etase concerning structure and catalytic properties. Phylogenetic stud ies suggested that both diverged from an ancestral glutamyl-tRNA synth etase responsible for the gluta-mylation of tRNA(Glu) and tRNA(Gln), a nd whose Glu-tRNA(Gln) product is transformed into Gln-tRNA(Gln) by a specific amidotransferase. This pathway is present in Gram-positive an d some Gram-negative eubacteria, in some archae and in organelles, and was never found jointly with a glutaminyl-tRNA synthetase. Other Gram -negative eubacteria and the cytoplasm of eukaryotes contain a glutamy l-tRNA synthetase specific for tRNA(Glu), and a glutaminyl-tRNA synthe tase. Bacterial glutamyl-tRNA synthetases consist of about 500 amino a cid residues, possess molecular masses of about 50 kDa, and act as mon omers. In higher eukaryotes chimeric glutamyl-prolyl-tRNA synthetases were found, in a high molecular mass complex containing several other aminoacyl-tRNA synthetases. To date one crystal structure of a glutamy l-tRNA synthetase (Thermus thermophilus) has been solved, The molecule has the form of a bent cylinder and consists of four domains. The N-t erminal half (domains 1 and 2) contains the 'Rossman fold' typical for class I synthetases and resembles the corresponding part of E. coli G lnRS, whereas the C-terminal half exhibits a GluRS-specific structure. As found for the other aminoacyl-tRNA synthetases the catalytic pathw ay of GluRS includes the formation of an aminoacyl adenylate in the fi rst reaction step, but GluRS shares a special property with GlnRS and ArgRS: the ATP/PPi pyrophosphate exchange reaction is only catalyzed i n the presence of the cognate tRNA. Compared with other aminoacyl-tRNA synthetases a relatively high number of investigations deals with rec ognition of tRNA(Glu) by GluRS. Besides interactions between the enzym e and the acceptor stem and the anticodon of tRNA(Glu), checking of th e dihydrouridine arm and of the variable loop by GluRS are documented.