InterPro domain: IPR002312

Aspartyl tRNA synthetase 6.1.1.12 is an alpha2 dimer that belongs to class IIb. Structural analysis combined with mutagenesis and enzymology data on the yeast enzyme point to a tRNA binding process that starts by a recognition event between the tRNA anticodon loop and the synthetase anticodon binding module [ 1 ].

Asparagine tRNA ligase ( 6.1.1.22 ) is also an alpha2 dimer that belongs to class IIb. There are remarkable similarities between the tertiary structures of asparaginyl-tRNA synthetase and aspartyl-tRNA synthetase [ 2 ].

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 [ 3 , 4 ]. These proteins differ widely in size and oligomeric state, and have limited sequence homology [ 5 ]. 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 [ 6 ]. Class II aminoacyl-tRNA synthetases share an anti-parallel beta-sheet fold flanked by alpha-helices [ 7 ], and are mostly dimeric or multimeric, containing at least three conserved regions [ 8 , 9 , 10 ]. 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 [ 11 ].

1. The free yeast aspartyl-tRNA synthetase differs from the tRNA(Asp)-complexed enzyme by structural changes in the catalytic site, hinge region, and anticodon-binding domain. J. Mol. Biol. 299, 1313-24
2. The crystal structure of asparaginyl-tRNA synthetase from Thermus thermophilus and its complexes with ATP and asparaginyl-adenylate: the mechanism of discrimination between asparagine and aspartic acid. EMBO J. 17, 2947-60
3. Aminoacyl-tRNA synthetases, the genetic code, and the evolutionary process. Microbiol. Mol. Biol. Rev. 64, 202-36
4. Aminoacyl-tRNA synthetases: versatile players in the changing theater of translation. RNA 8, 1363-72
5. Partition of tRNA synthetases into two classes based on mutually exclusive sets of sequence motifs. Nature 347, 203-6
6. The 2.0 A crystal structure of Thermus thermophilus methionyl-tRNA synthetase reveals two RNA-binding modules. Structure 8, 197-208
7. Structural basis for transfer RNA aminoacylation by Escherichia coli glutaminyl-tRNA synthetase. Biochemistry 32, 8758-71
8. The aminoacyl-tRNA synthetase family: modules at work. Bioessays 15, 675-87
9. Classes of aminoacyl-tRNA synthetases and the establishment of the genetic code. Trends Biochem. Sci. 16, 1-3
10. Sequence, structural and evolutionary relationships between class 2 aminoacyl-tRNA synthetases. Nucleic Acids Res. 19, 3489-98
11. 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