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 [PMID:2203971]. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold and are mostly monomeric [PMID:10673435], while class II aminoacyl-tRNA synthetases share an anti-parallel beta-sheet formation, flanked by alpha-helices [PMID:8364025], and are mostly dimeric or multimeric. 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 [PUB00015156].

The 10 class I synthetases are considered to have in common the catalytic domain structure based on the Rossmann fold, which is totally different from the class II catalytic domain structure. The class I synthetases are further divided into three subclasses, a, b and c, according to sequence homology. tRNA binding involves an alpha-helical structure that is conserved between class I and class II synthetases.

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 [PMID:2203971]. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold and are mostly monomeric [PMID:10673435], while class II aminoacyl-tRNA synthetases share an anti-parallel beta-sheet formation, flanked by alpha-helices [PMID:8364025], and are mostly dimeric or multimeric. 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 [PUB00015156].

The 10 class I synthetases are considered to have in common the catalytic domain structure based on the Rossmann fold, which is totally different from the class II catalytic domain structure. The class I synthetases are further divided into three subclasses, a, b and c, according to sequence homology. tRNA binding involves an alpha-helical structure that is conserved between class I and class II synthetases.

Leucyl tRNA synthetase (EC: 6.1.1.4) is an alpha monomer that belongs to class Ia. There are two different families of leucyl-tRNA synthetases. This family includes the eubacterial and mitochondrial synthetases. The crystal structure of leucyl-tRNA synthetase from the hyperthermophile Thermus thermophilus has an overall architecture that is similar to that of isoleucyl-tRNA synthetase, except that the putative editing domain is inserted at a different position in the primary structure. This feature is unique to prokaryote-like leucyl-tRNA synthetases, as is the presence of a novel additional flexibly inserted domain [PMID:10811626].