Insights into editing from an ile-tRNA synthetase structure with tRNAile and mupirocin. Science 285:1074–7. doi

IsoleucylÐtransfer RNA (tRNA) synthetase (IleRS) joins Ile to tRNAIle at its synthetic active site and hydrolyzes incorrectly acylated amino acids at its editing active site. The 2.2 angstrom resolution crystal structure of Staphylo-coccus aureus IleRS complexed with tRNAIle and Mupirocin shows the acceptor strand of the tRNAIle in the continuously stacked, A-form conformation with the 39 terminal nucleotide in the editing active site. To position the 39 terminus in the synthetic active site, the acceptor strand must adopt the hairpinned conformation seen in tRNAGln complexed with its synthetase. The amino acid editing activity of the IleRS may result from the incorrect products shuttling between the synthetic and editing active sites, which is reminiscent of the editing mechanism of DNA polymerases. The aminoacyl-tRNA synthetases that amino-acylate tRNAs with Ile, Thr, and Ala must discriminate against the amino acid containing one less methyl group. Based on thermodynam