7N8Y

Oxidized PheRS G318W from Salmonella enterica serovar Typhimurium

Summary for 7N8Y

• Entry DOI: 10.2210/pdb7n8y/pdb
• EMDB information: 24249
• Descriptor: Phenylalanine--tRNA ligase alpha subunit, Phenylalanine--tRNA ligase beta subunit (2 entities in total)
• Functional Keywords: synthetase, trna-binding protein, tetrameric, oxidized, rna binding protein, ligase
• Biological source: Salmonella enterica subsp. enterica serovar Typhimurium; More
• Total number of polymer chains: 4
• Total formula weight: 248569.06

Authors

Srinivas, P.,Dunham, C.M. (deposition date: 2021-06-16, release date: 2021-10-06, Last modification date: 2025-06-04)

Primary citation

Srinivas, P.,Steiner, R.E.,Pavelich, I.J.,Guerrero-Ferreira, R.,Juneja, P.,Ibba, M.,Dunham, C.M.
Oxidation alters the architecture of the phenylalanyl-tRNA synthetase editing domain to confer hyperaccuracy.
Nucleic Acids Res., 49:11800-11809, 2021

PubMed Abstract: High fidelity during protein synthesis is accomplished by aminoacyl-tRNA synthetases (aaRSs). These enzymes ligate an amino acid to a cognate tRNA and have proofreading and editing capabilities that ensure high fidelity. Phenylalanyl-tRNA synthetase (PheRS) preferentially ligates a phenylalanine to a tRNAPhe over the chemically similar tyrosine, which differs from phenylalanine by a single hydroxyl group. In bacteria that undergo exposure to oxidative stress such as Salmonella enterica serovar Typhimurium, tyrosine isomer levels increase due to phenylalanine oxidation. Several residues are oxidized in PheRS and contribute to hyperactive editing, including against mischarged Tyr-tRNAPhe, despite these oxidized residues not being directly implicated in PheRS activity. Here, we solve a 3.6 Å cryo-electron microscopy structure of oxidized S. Typhimurium PheRS. We find that oxidation results in widespread structural rearrangements in the β-subunit editing domain and enlargement of its editing domain. Oxidization also enlarges the phenylalanyl-adenylate binding pocket but to a lesser extent. Together, these changes likely explain why oxidation leads to hyperaccurate editing and decreased misincorporation of tyrosine. Taken together, these results help increase our understanding of the survival of S. Typhimurium during human infection.

PubMed: 34581811
DOI: 10.1093/nar/gkab856

Experimental method

ELECTRON MICROSCOPY (3.65 Å)