title: Redox status affects the catalytic activity of glutamyl-tRNA synthetase.
abstract: Glutamyl-tRNA synthetases (GluRS) provide Glu-tRNA for different processes including protein synthesis, glutamine transamidation and tetrapyrrole biosynthesis. Many organisms contain multiple GluRSs, but whether these duplications solely broaden tRNA specificity or also play additional roles in tetrapyrrole biosynthesis is not known. Previous studies have shown that GluRS1, one of two GluRSs from the extremophile Acidithiobacillus ferrooxidans, is inactivated when intracellular heme is elevated suggesting a specific role for GluRS1 in the regulation of tetrapyrrole biosynthesis. We now show that, in vitro, GluRS1 activity is reversibly inactivated upon oxidation by hemin and hydrogen peroxide. The targets for oxidation-based inhibition were found to be cysteines from a SWIM zinc-binding motif located in the tRNA acceptor helix-binding domain. tRNA(Glu) was able to protect GluRS1 against oxidative inactivation by hemin plus hydrogen peroxide. The sensitivity to oxidation of A. ferrooxidans GluRS1 might provide a means to regulate tetrapyrrole and protein biosynthesis in response to extreme changes in both the redox and heme status of the cell via a single enzyme.
authors.affiliation: Programa de Biología Celular y Molecular, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Chile.
authors.forename: Assaf
authors.initials: A
authors.lastname: Katz
authors.forename: Rajat
authors.initials: R
authors.lastname: Banerjee
authors.forename: Merly
authors.initials: M
authors.lastname: de Armas
authors.forename: Michael
authors.initials: M
authors.lastname: Ibba
authors.forename: Omar
authors.initials: O
authors.lastname: Orellana
mesh_terms: D042763:Acidithiobacillus / Q000201:enzymology*; D002384:Catalysis; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism; D005975:Glutamate-tRNA Ligase / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D006418:Heme / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction; D015032:Zinc / Q000737:chemistry / Q000378:metabolism
chemical_list: D006418:Heme; D005975:Glutamate-tRNA Ligase; D015032:Zinc; D003545:Cysteine