title: Modulation of substrate specificity within the amino acid editing site of leucyl-tRNA synthetase.
abstract: 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 Val338, which collectively fine-tune amino acid specificity to confer fidelity.
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, Texas 77204-5001, USA.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Zhai
authors.forename: Mir Hussain
authors.initials: MH
authors.lastname: Nawaz
authors.forename: Keun Woo
authors.initials: KW
authors.lastname: Lee
authors.forename: Erin
authors.initials: E
authors.lastname: Kirkbride
authors.forename: James M
authors.initials: JM
authors.lastname: Briggs
authors.forename: Susan A
authors.initials: SA
authors.lastname: Martinis
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites / Q000187:drug effects*; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D004252:DNA Mutational Analysis; D004926:Escherichia coli / Q000201:enzymology; D007935:Leucine-tRNA Ligase / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D013379:Substrate Specificity / Q000187:drug effects
chemical_list: D007935:Leucine-tRNA Ligase