InterPro: IPR002315 Glycyl-tRNA synthetase, alpha2 dimer

The aminoacyl-tRNA synthetases (EC:6.1.1.) 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 [1]. 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 [2]. Class II aminoacyl-tRNA synthetases share an anti-parallel beta-sheet fold flanked by alpha-helices [3], and are mostly dimeric or multimeric, containing at least three conserved regions [4, 5, 6]. However, tRNA binding involves an alpha-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 and valine belong to class I synthetases; these synthetases are further divided into three subclasses, a, b and c, according to sequence homology. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, lysine, phenylalanine, proline, serine, and threonine belong to class-II synthetases [7].

In eubacteria, glycyl-tRNA synthetase (EC:6.1.1.14) is an alpha2/beta2 tetramer composed of 2 different subunits [8, 9, 10]. In some eubacteria, in archaea and eukaryota, glycyl-tRNA synthetase is an alpha2 dimer, this family. It belongs to class IIc and is one of the most complex synthetases. What is most interesting is the lack of similarity between the two types: divergence at the sequence level is so great that it is impossible to infer descent from common genes. The alpha (see IPR002310) and beta subunits (see IPR002311) also lack significant sequence similarity. However, they are translated from a single mRNA [8], and a single chain glycyl-tRNA synthetase from Chlamydia trachomatis has been found to have significant similarity with both domains, suggesting divergence from a single polypeptide chain [10].

The sequence and crystal structure of the homodimeric glycyl-tRNA synthetase from Thermus thermophilus, shows that each monomer consists of an active site strongly resembling that of the aspartyl and seryl enzymes, a C-terminal anticodon recognition domain of 100 residues and a third domain unusually inserted between motifs 1 and 2 almost certainly interacting with the acceptor arm of tRNA(Gly). The C-terminal domain has a novel five-stranded parallel-antiparallel beta-sheet structure with three surrounding helices. The active site residues most probably responsible for substrate recognition, in particular in the Gly binding pocket, can be identified by inference from aspartyl-tRNA synthetase due to the conserved nature of the class II active site [11, 12].