9TJU

Ternary complex of E. coli leucyl-tRNA synthetase bound to tRNA(leu) and Leucinol in the editing state

Summary for 9TJU

• Entry DOI: 10.2210/pdb9tju/pdb
• Descriptor: Leucine--tRNA ligase, tRNA(leu), 1,2-ETHANEDIOL, ... (7 entities in total)
• Functional Keywords: leucine trna ligase antimicrobial target trna aminoacylation for protein translation, rna binding protein
• Biological source: Escherichia coli; More
• Total number of polymer chains: 2
• Total formula weight: 128231.45

Authors

Hoffmann, G.,Palencia, A. (deposition date: 2025-12-08, release date: 2026-08-05, Last modification date: 2026-08-19)

Primary citation

Hoffmann, G.,Dulic, M.,Gruic-Sovulj, I.,Palencia, A.
The ZN domain acts as a dynamic switch coordinating multiple-step aminoacylation in bacterial leucyl-tRNA synthetase.
Nucleic Acids Res., 54:-, 2026

PubMed Abstract: Aminoacyl-tRNA synthetases (AARSs) safeguard translational fidelity by coordinating amino acid activation and tRNA charging within distinct catalytic and editing domains. In leucyl-tRNA synthetase (LeuRS), the small, centrally located zinc-binding domain (ZN domain) sits at the crossroads of these functional centres, yet its role has remained enigmatic. Here, we present crystal structures of the Escherichia coli LeuRS-tRNALeu complex that capture the ZN domain in a previously unobserved conformation, revealing the pre-activation state. By integrating structural data with kinetic analysis, we propose a model for the aminoacylation reaction in which the ZN domain functions as a dynamic molecular switch that coordinates the different catalytic steps of the reaction cycle. We show that the ZN domain first acts as a wedge to prime the synthetic active site while locking the 3'-end tRNALeu in the editing domain. It subsequently reorients to stabilize the tRNA acceptor stem for aminoacyl transfer, before releasing it for proofreading. These findings resolve the mechanism of long-range domain communication in LeuRS and identify a discrete, druggable intermediate for the design of next-generation antimicrobials.

PubMed: 42573068
DOI: 10.1093/nar/gkag786

Experimental method

X-RAY DIFFRACTION (1.782 Å)