InterPro domain: IPR033911

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 ].

Methionine tRNA synthetase (MetRS, also known as methionine tRNA ligase), a class I aminoacyl-tRNA synthetases, aminoacylates the 2'-OH of the nucleotide at the 3' of the appropriate tRNA. MetRS, which consists of the core domain and an anti-codon binding domain, functions as a monomer. However, in some species the anti-codon binding domain is followed by an EMAP domain. In this case, MetRS functions as a homodimer. The core domain is based on the Rossman fold and is responsible for the ATP-dependent formation of the enzyme bound aminoacyl-adenylate. It contains the characteristic class I 'HIGH' and 'KMSKS' motifs, which are involved in ATP binding. As a result of a deletion event, MetRS has a significantly shorter core domain insertion than IleRS, ValRS, and LeuR. Consequently, the MetRS insertion lacks the editing function [ 10 ].

This entry represents the catalytic core domain of MetRS.

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. Structure and function of the C-terminal domain of methionyl-tRNA synthetase. Biochemistry 41, 13003-11