Glutamyl-Q tRNA(Asp) synthetase/Glutamate--tRNA ligase (GluQ/Sye)
Type: Family

This entry includes bacterial Glutamyl-Q tRNA(Asp) synthetases and Glutamate--tRNA ligase from eukaryotes and bacteria.

Glutamate-tRNA ligase (also known as glutamyl-tRNA synthetase;

) is a class I aminoacyl-tRNA synthetase. This enzyme shares similarities with glutaminyl-tRNA synthetase in terms of structure and catalytic properties. Glutamyl-tRNA synthetase (GluRS) and glutaminyl-tRNA synthetase (GlnRS) are grouped in the GlxRS subclass because of the shared evolutionary pathway of their catalytic domains. The catalytic domain of Glx subfamily is believed to be more ancient, having evolved from a common GluRS ancestor that contained only the catalytic domain. Anticodon binding domains of extant bacterial and eukaryotic/archeal GlxRS appeared independently at a later stage, with the anticodon-binding domain of bacterial GlnRS being acquired by an unique horizontal gene transfer event from the eukaryotic kingdom .

Bacterial GluRS are divided into two groups -discriminatory GluRS (D-GluRS) and non-discriminatory GluRS (ND-GluRS). While D-GluRS exclusively catalyses the transfer of Glu to tRNA(Glu), the ND-GluRS can also glutamylate tRNA(Gln) forming Glu-tRNAGln. The misacylated product is then transformed to Gln-tRNA(Gln) by an enzyme known as glutamyl-tRNA(Gln) amidotransferase. The bacterial GluRS structure consists of four domains. The N-terminal half (domains 1 and 2) contains the 'Rossman fold' typical for class I aminoacyl-tRNA synthetases and resembles the corresponding part of GlnRS, whereas the C-terminal half exhibits a GluRS-specific structural features .

Glutamyl-Q tRNA(Asp) synthetase resembles a shortened glutamyl-tRNA ligase, but its purpose is to modify tRNA(Asp) at a queuosine position in the anticodon rather than to charge a tRNA with its cognate amino acid . It catalyses the tRNA-independent activation of glutamate in presence of ATP and the subsequent transfer of glutamate onto the tRNA(Asp). In Escherichia coli, the glutamylated tRNA(Asp) might be involved in ribosomal protein biosynthesis, as it interacts with the elongation factor EF-Tu . Comparison of the three-dimensional structure of Glu-Q-RS with that of GluRS, both with a unique zinc-binding site, shows that a restricted number of residues determine the distinct catalytic properties of amino acid recognition and activation in both enzymes .

The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction . These proteins differ widely in size and oligomeric state, and have limited sequence homology . The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric . Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices , and are mostly dimeric or multimeric, containing at least three conserved regions . However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c .