<p>The aminoacyl-tRNA synthetases (<db_xref db="EC" dbkey="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 [<cite idref="PUB00007191"/>]. 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 [<cite idref="PUB00006477"/>]. Class II aminoacyl-tRNA synthetases share an anti-parallel beta-sheet fold flanked by alpha-helices [<cite idref="PUB00000386"/>], and are mostly dimeric or multimeric, containing at least three conserved regions [<cite idref="PUB00000723"/>, <cite idref="PUB00005365"/>, <cite idref="PUB00004391"/>]. 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. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, lysine, phenylalanine, proline, serine, and threonine belong to class-II synthetases [<cite idref="PUB00015156"/>]. 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.</p><p> Glutamyl-tRNA synthetase (<db_xref db="EC" dbkey="6.1.1.17"/>) is a class Ic synthetase and shows several similarities with glutaminyl-tRNA synthetase concerning structure and catalytic properties. It is an alpha2 dimer. To date one crystal structure of a glutamyl-tRNA synthetase (<taxon tax_id="274">Thermus thermophilus</taxon>) has been solved. The molecule has the form of a bent cylinder and consists of four domains. The N-terminal half (domains 1 and 2) contains the 'Rossman fold' typical for class I synthetases and resembles the corresponding part of <taxon tax_id="562">Escherichia coli</taxon> GlnRS, whereas the C-terminal half exhibits a GluRS-specific structure [<cite idref="PUB00006397"/>].</p>