InterPro domain: IPR012795

This entry represents the N-terminal domain of lysidine-tRNA(Ile) synthetase, which ligates lysine onto the cytidine present at position 34 of the AUA codon-specific tRNA(Ile) that contains the anticodon CAU, in an ATP-dependent manner. Cytidine is converted to lysidine, thus changing the amino acid specificity of the tRNA from methionine to isoleucine. The N-terminal region contains the highly conserved SGGXDS motif, predicted to be a PP-loop motif involved in ATP binding.

The only examples in which the wobble position of a tRNA must discriminate between G and A of mRNA are AUA (Ile) vs. AUG (Met) and UGA (stop) vs. UGG (Trp). In all bacteria, the wobble position of the tRNA(Ile) recognizing AUA is lysidine, a lysine derivative of cytidine. This domain is found, apparently, in all bacteria in a single copy. Eukaryotic sequences appear to be organellar. The domain architecture of this protein is variable; some, including characterised proteins of Escherichia coli and Bacillus subtilis known to be tRNA(Ile)-lysidine synthetase, include a conserved 50-residue domain that many other members lack. This protein belongs to the ATP-binding PP-loop family. It appears in the literature and protein databases as TilS, YacA, and putative cell cycle protein MesJ (a misnomer).

The PP-loop motif appears to be a modified version of the P-loop of nucleotide binding domain that is involved in phosphate binding [ 1 ]. Named PP-motif, since it appears to be a part of a previously uncharacterised ATP pyrophophatase domain. ATP sulfurylases, E. coli NtrL, and B. subtilis OutB consist of this domain alone. In other proteins, the pyrophosphatase domain is associated with amidotransferase domains (type I or type II), a putative citrulline-aspartate ligase domain or a nitrilase/amidase domain. The HUP domain class (after HIGH-signature proteins, UspA, and PP-ATPase) groups together PP-loop ATPases, the nucleotide-binding domains of class I aminoacyl-tRNA synthetases, UspA protein (USPA domains), photolyases, and electron transport flavoproteins (ETFP). The HUP domain is a distinct class of alpha/beta domain[ 2 ].

1. A P-loop-like motif in a widespread ATP pyrophosphatase domain: implications for the evolution of sequence motifs and enzyme activity. Proteins 20, 347-55
2. Monophyly of class I aminoacyl tRNA synthetase, USPA, ETFP, photolyase, and PP-ATPase nucleotide-binding domains: implications for protein evolution in the RNA. Proteins 48, 1-14