{
    "abstract": "Ferroptosis is a regulated form of cell death driven by lipid peroxidation, with 15-lipoxygenase (15LOX) enzyme playing a critical role in catalyzing the oxygenation of polyunsaturated fatty acid-containing phospholipids, such as 1-stearoyl-2-arachidonoyl-sn-glycero-3-phosphoethanolamine (SAPE), to initiate this process. The molecular oxygen required for this catalytic reaction is subject to continuous competition among various oxygen-consuming enzymes, which influences the efficiency of lipid peroxidation. In this study, we utilized structure-based modeling and all-atom molecular dynamics simulations to explore the oxygen diffusion pathways in 15LOX-1 under varying oxygen concentrations and in the presence of key components, including a substrate, binding partner PE-binding protein 1 (PEBP1), and the membrane environment. Extensive computational experiments were performed on various system configurations, examining the role of substrate binding, membrane presence, and PEBP1 association in oxygen acquisition. Our computational results indicate that the substrate binding induces a conformational change in 15LOX-1, facilitating the simultaneous recruitment of one or two O",
    "authors": [
        {
            "affiliation": "Institute of Physics, Faculty of Physics, Astronomy and Informatics, Nicolaus Copernicus University in Torun, PL87100, Torun, Poland.",
            "firstname": "Thiliban",
            "initials": "T",
            "lastname": "Manivarma"
        },
        {
            "affiliation": "Institute of Physics, Faculty of Physics, Astronomy and Informatics, Nicolaus Copernicus University in Torun, PL87100, Torun, Poland.",
            "firstname": "Wieslaw",
            "initials": "W",
            "lastname": "Nowak"
        },
        {
            "affiliation": "Department of Environmental and Occupational Health, Center for Free Radical and Antioxidant Health, School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA.",
            "firstname": "Yulia Y",
            "initials": "YY",
            "lastname": "Tyurina"
        },
        {
            "affiliation": "Department of Environmental and Occupational Health, Center for Free Radical and Antioxidant Health, School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA.",
            "firstname": "Vladimir A",
            "initials": "VA",
            "lastname": "Tyurin"
        },
        {
            "affiliation": "Department of Environmental and Occupational Health, Center for Free Radical and Antioxidant Health, School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA; Department of Pediatrics, Division of Critical Care and Hospital Medicine, Redox Health Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, 10032, USA.",
            "firstname": "H\u00fclya",
            "initials": "H",
            "lastname": "Bayir"
        },
        {
            "affiliation": "Department of Environmental and Occupational Health, Center for Free Radical and Antioxidant Health, School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA; Department of Pediatrics, Division of Critical Care and Hospital Medicine, Redox Health Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, 10032, USA; Department of Radiation Oncology, University of Pittsburgh, Pittsburgh, PA, 15213, USA; Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, 15260, USA; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, 15261, USA.",
            "firstname": "Valerian E",
            "initials": "VE",
            "lastname": "Kagan"
        },
        {
            "affiliation": "Institute of Physics, Faculty of Physics, Astronomy and Informatics, Nicolaus Copernicus University in Torun, PL87100, Torun, Poland. Electronic address: karolamik@fizyka.umk.pl.",
            "firstname": "Karolina",
            "initials": "K",
            "lastname": "Mikulska-Ruminska"
        }
    ],
    "conclusions": null,
    "copyrights": "Copyright \u00a9 2025 The Authors. Published by Elsevier B.V. All rights reserved.",
    "doi": "10.1016/j.redox.2025.103636",
    "journal": "Redox biology",
    "keywords": [
        "15-Lipoxygenase",
        "Ferroptosis",
        "Ligand transport",
        "PEBP1",
        "Phospholipids",
        "molecular dynamics"
    ],
    "methods": null,
    "publication_date": "2025-04-18",
    "pubmed_id": "40245701",
    "results": null,
    "title": "The presence of substrate warrants oxygen access tunnels toward the catalytic site of lipoxygenases.",
    "xml": "<Element 'PubmedArticle' at 0x7885028f3920>"
}