InterPro domain: IPR002302

Leucine-tRNA ligase ( 6.1.1.4 ) is an alpha monomer that belongs to class Ia. The crystal structure of leucine-tRNA ligase from the hyperthermophile Thermus thermophilus has an overall architecture that is similar to that of isoleucine-tRNA ligase, except that the putative editing domain is inserted at a different position in the primary structure. This feature is unique to prokaryote-like leucine-tRNA ligases, as is the presence of a novel additional flexibly inserted domain [ 1 ].

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 [ 2 , 3 ]. These proteins differ widely in size and oligomeric state, and have limited sequence homology [ 4 ]. 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 [ 5 ]. Class II aminoacyl-tRNA synthetases share an anti-parallel beta-sheet fold flanked by alpha-helices [ 6 ], and are mostly dimeric or multimeric, containing at least three conserved regions [ 7 , 8 , 9 ]. 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 [ 10 ].

1. The 2 A crystal structure of leucyl-tRNA synthetase and its complex with a leucyl-adenylate analogue. EMBO J. 19, 2351-61
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3. Aminoacyl-tRNA synthetases: versatile players in the changing theater of translation. RNA 8, 1363-72
4. Partition of tRNA synthetases into two classes based on mutually exclusive sets of sequence motifs. Nature 347, 203-6
5. The 2.0 A crystal structure of Thermus thermophilus methionyl-tRNA synthetase reveals two RNA-binding modules. Structure 8, 197-208
6. Structural basis for transfer RNA aminoacylation by Escherichia coli glutaminyl-tRNA synthetase. Biochemistry 32, 8758-71
7. The aminoacyl-tRNA synthetase family: modules at work. Bioessays 15, 675-87
8. Classes of aminoacyl-tRNA synthetases and the establishment of the genetic code. Trends Biochem. Sci. 16, 1-3
9. Sequence, structural and evolutionary relationships between class 2 aminoacyl-tRNA synthetases. Nucleic Acids Res. 19, 3489-98
10. 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