{
  "abstract": "Phosphoglycerate kinase 1 (PGK1) is a key metabolic enzyme responsible for ATP production, and its dysregulation is linked to the Warburg effect in cancer and to neurodegenerative diseases such as Parkinson's. Recent studies indicate that terazosin, an FDA-approved drug, enhances PGK1-mediated ATP production. However, X-ray crystallography indicates that terazosin binds at a site that partially overlaps the nucleotide-binding site, thereby inhibiting PGK1. In this study, we employed solution-state nuclear magnetic resonance (NMR) chemical shift titrations to confirm that terazosin binds at a site that partially overlaps the nucleotide-binding pocket of PGK1, stabilizing the enzyme in its open conformation, which is accessible to substrates and products. This binding shifts the equilibrium toward the open state, enhancing product release at low concentrations while blocking substrate binding at higher concentrations. These findings are strengthened by the 3D NMR2 structure determination of the PGK1-terazosin complex, using selective unlabeling combined with subsequent partial amino acid assignments, which validates the available X-ray structure.",
  "abstract_shown": true,
  "affiliations": [
    "Institute for Molecular Physical Science, Vladimir Prelog Weg 2, 8093 Zürich, Switzerland.",
    "Department of Pharmaceutical Sciences, University of Vienna, Josef-Holaubek-Platz 2, A-1090 Vienna, Austria.",
    "NexMR AG, Wiesenstrasse 10A, 8952 Schlieren, Switzerland."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Matthias Bütikofer",
      "orcid": "0000-0002-7900-8288"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Felix Torres"
    },
    {
      "affs": [
        0
      ],
      "name": "Dhiman Ghosh"
    },
    {
      "affs": [
        0
      ],
      "name": "Nils Lorz"
    },
    {
      "affs": [
        0
      ],
      "name": "Roland Riek"
    },
    {
      "affs": [
        1
      ],
      "name": "Julien Orts",
      "orcid": "0000-0003-3287-1532"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/945wx22cycy41.bib",
  "cited_by": 0,
  "doi": "10.1021/jacsau.6c00823",
  "fulltext_url": "https://europepmc.org/articles/PMC13714833",
  "id": "945wx22cycy41",
  "issns": [
    "2691-3704"
  ],
  "landing_url": "https://europepmc.org/article/MED/42953203",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1607|Advanced NMR Techniques and Applications"
    ]
  ],
  "openalex": "W7214153141",
  "pdf_url": "https://europepmc.org/articles/PMC13714833?pdf=render",
  "pmcid": "PMC13714833",
  "pmid": "42953203",
  "published": "2026-09-24",
  "publisher": "American Chemical Society",
  "ris": "https://research.draconitic.com/paper/945wx22cycy41.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:41Z",
      "native_id": "MED:42953203",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42953203"
    },
    {
      "first_seen": "2026-11-01T12:22:15Z",
      "native_id": "PMC13714833",
      "source": "pmc",
      "url": "https://doi.org/10.1021/jacsau.6c00823"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1607|Advanced NMR Techniques and Applications",
      "subfield": "physical"
    }
  ],
  "title": "Terazosin Activates or Inhibits Human Phosphoglycerate Kinase 1 on a Dose-Dependent Basis: Mechanistic and Structural Insights by NMR.",
  "title_text": "Terazosin Activates or Inhibits Human Phosphoglycerate Kinase 1 on a Dose-Dependent Basis: Mechanistic and Structural Insights by NMR.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:22:15Z",
  "url": "https://research.draconitic.com/paper/945wx22cycy41",
  "venue": "JACS Au",
  "versions": []
}