{
  "abstract": "The New Delhi metallo‑β‑lactamase 1 (NDM‑1) is a major driver of carbapenem resistance in Gram‑negative pathogens, yet the molecular basis by which antimicrobial peptides inhibit this enzyme has remained unresolved. Here, we combine high‑resolution NMR spectroscopy, CSP-driven HADDOCK docking, intermolecular NOE cross-validation, and molecular dynamics simulations to reveal a distinct zinc-retaining dynamic allosteric mechanism. Thanatin binds adjacent to the catalytic groove, preserving the native di‑zinc coordination environment while simultaneously restricting the dynamics of the L3 catalytic loop, as confirmed by Zn‑bound spectral fingerprints and EDTA titration experiments. Real-time NMR and spectrophotometric kinetics confirm that this dynamic restriction induces a dose-dependent functional inhibition, structurally explained by a L3-loop displacement that prevents optimal substrate accommodation. This conformational restriction explains how the peptide inhibits the enzyme while maintaining a zinc-bound but catalytically compromised state, a finding that reconciles prior macroscopic biochemical observations with a new atomic-level structural model. In bacterial assays, this allosteric inhibition translates to a moderate restoration of carbapenem sensitivity, resulting in a 50% reduction in viable cell output even under high-level enzyme expression. Our findings help define a mechanistic framework for designing next‑generation peptide inhibitors that target the dynamic vulnerabilities of metallo‑β‑lactamases.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "Gwladys Rivière",
      "orcid": "0000-0002-4488-2813"
    },
    {
      "name": "Prince Kumar"
    },
    {
      "name": "Thomas Cummins"
    },
    {
      "name": "Ansel Hsiao",
      "orcid": "0000-0002-0258-6960"
    },
    {
      "name": "Leonard J. Mueller"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5mbv3xsqgpdbh.bib",
  "cited_by": 0,
  "doi": "10.1038/s42004-026-02259-1",
  "fulltext_url": null,
  "id": "5mbv3xsqgpdbh",
  "issns": [
    "2399-3669"
  ],
  "landing_url": "https://www.nature.com/articles/s42004-026-02259-1",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-02",
  "publisher": "Springer Science and Business Media LLC",
  "ris": "https://research.draconitic.com/paper/5mbv3xsqgpdbh.ris",
  "sources": [
    {
      "first_seen": "2026-11-02T18:20:53Z",
      "native_id": "10.1038/s42004-026-02259-1",
      "source": "feed-nature",
      "url": "https://www.nature.com/articles/s42004-026-02259-1"
    },
    {
      "first_seen": "2026-11-03T00:20:56Z",
      "native_id": "10.1038/s42004-026-02259-1",
      "source": "crossref",
      "url": "https://www.nature.com/articles/s42004-026-02259-1"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "issn:2399-3669",
      "subfield": "general"
    }
  ],
  "title": "Allosteric inhibition of NDM-1 by thanatin preserves the di-zinc center while restricting dynamics",
  "title_text": "Allosteric inhibition of NDM-1 by thanatin preserves the di-zinc center while restricting dynamics",
  "type": "peer-reviewed",
  "updated_at": "2026-11-04T00:21:39Z",
  "url": "https://research.draconitic.com/paper/5mbv3xsqgpdbh",
  "venue": "Communications Chemistry",
  "versions": []
}