InterPro domain: IPR014758

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 ligase ( 6.1.1.10 ) is an alpha 2 dimer. In some species (archaea, eubacteria and eukaryotes) a coding sequence, similar to the C-terminal end of MetRS, is present as an independent gene which is a tRNA binding domain as a dimer. In eubacteria, MetRS can also be split in two sub-classes corresponding to the presence of one or two CXXC domains specific to zinc binding. The crystal structures of a number of methionine-tRNA ligases are known [ 10 , 10 , 11 ].

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