InterPro: IPR002313 Lysyl-tRNA synthetase, class II

The aminoacyl-tRNA synthetases (EC:6.1.1.) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction. These proteins differ widely in size and oligomeric state, and have limited sequence homology [1]. 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 [2]. Class II aminoacyl-tRNA synthetases share an anti-parallel beta-sheet fold flanked by alpha-helices [3], and are mostly dimeric or multimeric, containing at least three conserved regions [4, 5, 6]. 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 and valine belong to class I synthetases; these synthetases are further divided into three subclasses, a, b and c, according to sequence homology. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, lysine, phenylalanine, proline, serine, and threonine belong to class-II synthetases [7].

Lysyl-tRNA synthetase (EC:6.1.1.6) is an alpha 2 homodimer that belong to both class I and class II. In eubacteria and eukaryota lysyl-tRNA synthetases belong to class II in the same family as aspartyl tRNA synthetase. The class Ic lysyl-tRNA synthetase family is present in archaea and some eubacteria [8]. Moreover in some eubacteria there is a gene X, which is similar to a part of lysyl-tRNA synthetase from class II. Lysyl-tRNA synthetase is duplicated in some species with, for example in Escherichia coli, as a constitutive gene (lysS) and an induced one (lysU). No residues are directly involved in catalysis, but a number of highly conserved amino acids and three metal ions coordinate the substrates and stabilise the pentavalent transition state. Lysine is activated by being attached to the alpha-phosphate of AMP before being transferred to the cognate tRNA. The refined crystal structures give "snapshots" of the active site corresponding to key steps in the aminoacylation reaction and provide the structural framework for understanding the mechanism of lysine activation. The active site of LysU is shaped to position the substrates for the nucleophilic attack of the lysine carboxylate on the ATP alpha-phosphate. No residues are directly involved in catalysis, but a number of highly conserved amino acids and three metal ions coordinate the substrates and stabilise the pentavalent transition state. A loop close to the catalytic pocket, disordered in the lysine-bound structure, becomes ordered upon adenine binding [9].