Editing domain 1a

The post-transfer editing domain LIV (Edit-LIV) catalyzes the removal of misacylated residues $X$ from the cognate acceptor stems of isoleucine, leucine, and valine: $ X\text{-tRNA}^\text{Ile} \xrightarrow{\text{Edit-LIV}} X + \text{tRNA}^\text{Ile} $ $ X\text{-tRNA}^\text{Leu} \xrightarrow{\text{Edit-LIV}} X + \text{tRNA}^\text{Leu} $ $ X\text{-tRNA}^\text{Val} \xrightarrow{\text{Edit-LIV}} X + \text{tRNA}^\text{Val} $ The domain appears within the catalytic domains of [IleRS](/class1/ile), [ValRS](/class1/val), and the two forms of LeuRS: [LeuRS-A](/class1/leu2) and [LeuRS-B](/class1/leu1). This provides further amino acid selectivity by expelling a wide range of mistargetted amino acids such alanine, cysteine, threonine, valine, isoleucine, methionine, homocysteine, and norvaline (Gomez and Ibba, 2020). ValRS also targets misactivated amino acids, such as threonine, through pre-transfer editing activity (Fersht et al. 1976). Its discrimination first against size (i.e. by filtering out isoleucine), and second against polarity (i.e. removal of misactivated threonine) has been described as a double-sieve mechanism (Fersht et al. 1976, Fukai et al. 2000). Interestingly, the domain resides in two different parts of the catalytic domain's primary sequence: upstream of the CP2 insertion for ValRS, IleRS, and LeuRS-A, and downstream of CP2 in the case of the bacterial-like form LeuRS-B (Fukunaga et al. 2005).

References

Gomez, Miguel Angel Rubio, and Michael Ibba. "Aminoacyl-tRNA synthetases." Rna 26.8 (2020): 910-936. Nureki, Osamu, et al. "Enzyme structure with two catalytic sites for double-sieve selection of substrate." Science 280.5363 (1998): 578-582. Silvian, Laura F., Jimin Wang, and Thomas A. Steitz. "Insights into editing from an ile-tRNA synthetase structure with tRNAile and mupirocin." Science 285.5430 (1999): 1074-1077. Fukunaga, Ryuya, and Shigeyuki Yokoyama. "Crystal structure of leucyl-tRNA synthetase from the archaeon Pyrococcus horikoshii reveals a novel editing domain orientation." Journal of molecular biology 346.1 (2005): 57-71. Fukai, Shuya, et al. "Structural basis for double-sieve discrimination of L-valine from L-isoleucine and L-threonine by the complex of tRNAVal and valyl-tRNA synthetase." Cell 103.5 (2000): 793-803. Fersht, Alan R., and Meredith M. Kaethner. "Enzyme hyperspecificity. Rejection of threonine by the valyl-tRNA synthetase by misacylation and hydrolytic editing." Biochemistry 15.15 (1976): 3342-3346.