PROSITE documentation PDOC00363

Aminoacyl-transfer RNA synthetases class-II profiles

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.

The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, lysine, phenylalanine, proline, serine, and threonine are referred to as class-II synthetases [2,3,4,5,6]. Class-II enzymes are generally dimeric or tetrameric, and attach their amino acid to the 3' OH of their tRNA, except for phenylalaninyl-tRNA synthetase which uses the 2' OH like the class-I tRNA synthetase.

Class-II tRNA synthetases are structurally distinct from the class-I enzymes and have a central antiparallel β-sheet instead of the Rossman fold found in Class-I structure (see <PDB:1SES>) [8].

Class-II tRNA synthetases do not share a high degree of similarity, however at least three conserved regions are present [2,5,9]. We have developed three profiles to detect class-II tRNA synthetases. The first one recognize all class-II enzymes except for heterodimeric glycyl-tRNA synthetases and alanyl-tRNA synthetases which are picked up by specific profiles.

There are at least two families of proteins related to class-II enzymes and that are also recognized by the first profile.

• Bacterial aspartate--ammonia ligase (EC 6.3.1.1), the enzyme that produces asparagine from aspartate [10].
• Bacterial ATP phosphoribosyltransferase regulatory subunit (gene hisZ). HisZ seems to allow the regulation of ATP phosphoribosyltransferase activity by histidine. It is distantly related to histidyl-tRNA synthetases and not all members of this family are picked up by the profile.