{
  "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.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "name": "Guillaume Hoffmann"
    },
    {
      "name": "Morana Dulić"
    },
    {
      "name": "Ita Gruic-Sovulj"
    },
    {
      "name": "Andrés Palencia"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6mq8m6hbc1xrk.bib",
  "cited_by": 0,
  "doi": "10.1093/nar/gkag786",
  "fulltext_url": null,
  "id": "6mq8m6hbc1xrk",
  "issns": [
    "0305-1048",
    "1362-4962"
  ],
  "landing_url": "https://hal.science/hal-05771703v1",
  "language": "en",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.chim"
    ],
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "1312|RNA and protein synthesis mechanisms"
    ]
  ],
  "openalex": "W7202116553",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-27",
  "publisher": "Oxford University Press",
  "ris": "https://research.draconitic.com/paper/6mq8m6hbc1xrk.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:44Z",
      "native_id": "hal-05771703",
      "source": "hal",
      "url": "https://hal.science/hal-05771703v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|RNA and protein synthesis mechanisms",
      "subfield": "molecular-biology"
    }
  ],
  "title": "The ZN domain acts as a dynamic switch coordinating multiple-step aminoacylation in bacterial leucyl-tRNA synthetase",
  "title_text": "The ZN domain acts as a dynamic switch coordinating multiple-step aminoacylation in bacterial leucyl-tRNA synthetase",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:44Z",
  "url": "https://research.draconitic.com/paper/6mq8m6hbc1xrk",
  "venue": "Nucleic Acids Research",
  "versions": []
}