Aminoacyl-tRNA synthetases (EC 6.1.1.-) [1] are a group of enzymes which activate amino acids and transfer them to specific tRNA molecules as the first step in protein biosynthesis. In prokaryotic organisms there are at least twenty different types of aminoacyl-tRNA synthetases, one for each different amino acid. In eukaryotes there are generally two aminoacyl-tRNA synthetases for each different amino acid: one cytosolic form and a mitochondrial form. While all these enzymes have a common function, they are widely diverse in terms of subunit size and of quaternary structure.

A few years ago it was found [2] that several aminoacyl-tRNA synthetases share a region of similarity in their N-terminal section, in particular the consensus tetrapeptide His-Ile-Gly-His ('HIGH') is very well conserved. The 'HIGH' region has been shown [3] to be part of the adenylate binding site. The 'HIGH' signature has been found in the aminoacyl-tRNA synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, and valine. These aminoacyl-tRNA synthetases are referred to as class-I synthetases [4,5,6] and seem to share the same tertiary structure based on a Rossmann fold.