| Description: |
This superfamily represents the fold comprising the seven β-strands found in the catalytic domain of Class II of aminoacyl-tRNA synthetases (aaRS), the lipoyl protein ligase (LPL) and the biotinyl protein ligase (BPL). Interestingly, Class II of aaRSs has a two-step reaction mechanism analogous to that of BPL. It first catalyses the ATP-dependent formation of an aminoacyl-AMP intermediate and then transfer the activated aminoacyl moiety to an acceptor tRNA [].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 [, ]. These proteins differ widely in size and oligomeric state, and have limited sequence homology []. 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 []. Class II aminoacyl-tRNA synthetases share an antiparallel β-sheet fold flanked by α-helices [], and are mostly dimeric or multimeric, containing at least three conserved regions [, , ]. However, tRNA binding involves an α-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 [].BPLs and LPLs are evolutionarily related protein families, with a homologous catalytic module (seven-stranded mixed β-sheet on one side and four α-helices on the other side) that must have evolved from a common ancestor [, ]. Amino acid sequence conservation between the catalytic modules of biotinyl protein ligases (BPLs) and lipoyl protein ligases (LPLs) is very low, and mainly affects residues that are important for the scaffold of the structure, such as those contributing to the hydrophobic core. Despite the poor overall sequence similarity, a single lysine residue is strictly conserved in all LPL and BPL sequences. This lysine residue is likely to bind specifically to the carbonyl oxygen of the carboxyl group of biotin or at the end of the hydrogen-carbon tail of the lipoyl moiety []. |
