InterPro domain: IPR009008

Certain aminoacyl-tRNA synthetases prevent potential errors in protein synthesis through deacylation of mischarged tRNAs. The close homologues isoleucyl-tRNA synthetase (IleRS) and valyl-tRNA synthetase (ValRS) deacylate Val-tRNAIle and Thr-tRNAVal, respectively. These reactions strictly require the presence of the cognate tRNA. In the absence of tRNA, the enzymatically generated misactivated adenylates remain in the active site, sequestered from hydrolysis. Upon addition of cognate tRNA the misactivated amino acids are hydrolysed, regenerating the free tRNA and amino acid, while converting 1 equivalent of ATP to AMP. A prominent mechanism for editing misactivated amino acids is the rapid hydrolysis of transiently mischarged tRNA. This reaction is catalysed at a second active site on IleRS and ValRS. This site is located within a large insertion (termed CP1) into the canonical class I aminoacyl-tRNA synthetase active-site fold [ 1 , 2 ]. The CP1 domain as an isolated polypeptide hydrolyses its cognate mischarged tRNA [ 3 ].

1. Structural basis for substrate recognition by the editing domain of isoleucyl-tRNA synthetase. J. Mol. Biol. 359, 901-12
2. Leucyl-tRNA synthetase editing domain functions as a molecular rheostat to control codon ambiguity in Mycoplasma pathogens. Proc. Natl. Acad. Sci. U.S.A. 110, 3817-22
3. Plasticity of recognition of the 3'-end of mischarged tRNA by class I aminoacyl-tRNA synthetases. J. Biol. Chem. 277, 20510-7