InterPro domain: IPR004530

The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction [ 1 , 2 ]. These proteins differ widely in size and oligomeric state, and have limited sequence homology [ 3 ]. 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 [ 4 ]. Class II aminoacyl-tRNA synthetases share an anti-parallel beta-sheet fold flanked by alpha-helices [ 5 ], and are mostly dimeric or multimeric, containing at least three conserved regions [ 6 , 7 , 8 ]. 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, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. 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 [ 9 ].

Phenylalanyl-tRNA synthetase ( 6.1.1.20 ) is an alpha2/beta2 tetramer composed of 2 subunits that belongs to class IIc. In eubacteria, a small subunit (pheS gene) can be designated as beta (E. coli) or alpha subunit (nomenclature adopted in InterPro). Reciprocally the large subunit(pheT gene) can be designated as alpha (E. coli) or beta (see IPR004531 and IPR004532 ). In all other kingdoms the two subunits have equivalent length in eukaryota, and can be identified by specific signatures. The enzyme from Thermus thermophilus has an alpha 2 beta 2 type quaternary structure and is one of the most complicated members of the synthetase family. Identification of phenylalanyl-tRNA synthetase as a member of class II aaRSs was based only on sequence alignment of the small alpha-subunit with other synthetases [ 10 ].

This family describes the mitochondrial phenylalanyl-tRNA synthetases. Unlike all other known phenylalanyl-tRNA synthetases, the mitochondrial form demonstrated from yeast is monomeric. It is similar to but longer than the alpha subunit (PheS) of the alpha 2 beta 2 form found in bacteria, Archaea, and eukaryotes, and shares the characteristic motifs of class II aminoacyl-tRNA ligases.

1. Aminoacyl-tRNA synthetases, the genetic code, and the evolutionary process. Microbiol. Mol. Biol. Rev. 64, 202-36
2. Aminoacyl-tRNA synthetases: versatile players in the changing theater of translation. RNA 8, 1363-72
3. Partition of tRNA synthetases into two classes based on mutually exclusive sets of sequence motifs. Nature 347, 203-6
4. The 2.0 A crystal structure of Thermus thermophilus methionyl-tRNA synthetase reveals two RNA-binding modules. Structure 8, 197-208
5. Structural basis for transfer RNA aminoacylation by Escherichia coli glutaminyl-tRNA synthetase. Biochemistry 32, 8758-71
6. The aminoacyl-tRNA synthetase family: modules at work. Bioessays 15, 675-87
7. Classes of aminoacyl-tRNA synthetases and the establishment of the genetic code. Trends Biochem. Sci. 16, 1-3
8. Sequence, structural and evolutionary relationships between class 2 aminoacyl-tRNA synthetases. Nucleic Acids Res. 19, 3489-98
9. Evolution of aminoacyl-tRNA synthetases--analysis of unique domain architectures and phylogenetic trees reveals a complex history of horizontal gene transfer events. Genome Res. 9, 689-710
10. Phenylalanyl-tRNA synthetase from Thermus thermophilus has four antiparallel folds of which only two are catalytically functional. Biochimie 75, 1091-8