9JKL

LYSYL-TRNA SYNTHETASE(LysRS) COMPLEXED WITH LYSINE

Summary for 9JKL

• Entry DOI: 10.2210/pdb9jkl/pdb
• Descriptor: Lysine--tRNA ligase, LYSINE, GLYCEROL, ... (4 entities in total)
• Functional Keywords: trna synthetase trna ligase lysyl-trna synthetase, ligase
• Biological source: Staphylococcus aureus subsp. aureus Mu50
• Total number of polymer chains: 1
• Total formula weight: 60636.31

Authors

Jani, J.,Mochi, J.,Shah, S.,Das, A.,Patel, D.,Pananghat, G.,Pappachan, A. (deposition date: 2024-09-16, release date: 2025-09-10, Last modification date: 2026-03-25)

Primary citation

Jani, J.,Mochi, J.,Shah, S.,Das, A.,Patel, D.,Pananghat, G.,Pappachan, A.
Unravelling the plasticity of substrate recognition by Staphylococcus aureus lysyl-tRNA synthetase and its implications for misacylation.
Febs J., 292:5835-5854, 2025

PubMed Abstract: Transfer RNA (tRNA) misacylation is a widespread phenomenon that affects translational fidelity due to the incorporation of non-cognate amino acids into proteins. We investigated the structural basis for the misacylation of tRNA by Staphylococcus aureus lysyl-tRNA synthetase (SaLysRS). Activity studies showed that SaLysRS misacylated tRNA with methionine and arginine. In vivo studies and MALDI-TOF analysis revealed the utilisation of these mischarged tRNAs in protein translation, as deciphered from the incorporation of non-cognate methionine and arginine into proteins. The misincorporation was also detrimental to cell growth. The three-dimensional structure of SaLysRS with its cognate substrate lysine was resolved at 2.3 Å resolution, which revealed key residues and conserved motifs needed for substrate recognition. Structural and mutational analysis and molecular dynamics simulations identified Glu233, Tyr273 and Glu420 as crucial residues for both cognate and non-cognate ligand binding. These insights, well-supported by structural, biochemical and computational data, enhance our knowledge of the mechanisms underlying misacylation in tRNA synthetases and its implications for cell growth.

PubMed: 40622075
DOI: 10.1111/febs.70185

Experimental method

X-RAY DIFFRACTION (2.3 Å)