Modulation of substrate specificity within the amino acid editing site of leucyl-tRNA synthetase

Yuxin Zhai, Mir Hussain Nawaz, Keun Woo Lee, Erin Kirkbride, James M. Briggs, Susan A. Martinis

Research output: Contribution to journalArticlepeer-review


The aminoacyl-tRNA synthetases covalently link transfer RNAs to their cognate amino acids. Some of the tRNA synthetases have evolved editing mechanisms to ensure fidelity in this first step of protein synthesis. The amino acid editing site for leucyl- (LeuRS) and isoleucyl- (IleRS) tRNA synthetases reside within homologous CP1 domains. In each case, a threonine-rich peptide and a second conserved GTG region that are separated by about 100 amino acids comprise parts of the hydrolytic editing site. While a number of sites are conserved between these two enzymes and likely confer a commonality to the mechanisms, some positions are idiosyncratic to LeuRS or IleRS. Herein, we provide evidence that a conserved arginine and threonine at respective sites in LeuRS and IleRS diverged to confer amino acid substrate recognition. This site complements other sites in the amino acid binding pocket of the editing active site of Escherichia coli LeuRS, including Thr252 and Val 338, which collectively fine-tune amino acid specificity to confer fidelity.

Original languageEnglish (US)
Pages (from-to)3331-3337
Number of pages7
Issue number11
StatePublished - Mar 20 2007

ASJC Scopus subject areas

  • Biochemistry


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