{
  "abstract": "Methionine sulfoxide reductase A (MsrA) protects proteins from oxidative damage through cysteine-based redox cycling, but how mammalian MsrA is structurally regulated during oxidation and reductive recycling has remained unclear. We report three crystal structures of mouse MsrA (mMsrA) that capture distinct redox states - reduced (3.0 Å), BME-trapped intermediate-like (BTIL; 1.6 Å), and oxidized (1.9 Å) - and reveal an unrecognized layer of regulation centered on Cys107. The BTIL structure visualizes catalytic Cys72 as a mixed disulfide with β-mercaptoethanol (BME) alongside a sulfenic acid at Cys107, a configuration not previously observed. The oxidized structure resolves the canonical Cys72-Cys218 disulfide together with an unexpected Cys107-Cys227 pairing that locks a C-terminal loop into a cap over the active site. LC-MS/MS mapping, MD simulations, activity assays, and thioredoxin (Trx)-trapping experiments converge on a model in which Cys72 drives catalysis, while Cys107-mediated disulfide rearrangement and Cys227-directed Trx entry gate substrate access and enzymatic regeneration - defining a noncanonical oxidized state that expands the mechanistic repertoire of mammalian MsrA under oxidative stress.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biotechnology, College of Life Sciences & Biotechnology, Korea University, Seoul, 02841, Republic of Korea.",
    "Intercollege, Hanyang University, Seoul, 04763, Republic of Korea; School of Environment and Science, Griffith University, Brisbane, QLD, 4111, Australia.",
    "School of Environment and Science, Griffith University, Brisbane, QLD, 4111, Australia.",
    "School of Environment and Science, Griffith University, Brisbane, QLD, 4111, Australia; Institute for Biomedicine and Glycomics, Griffith University, Brisbane, QLD, 4111, Australia. Electronic address: K.Tonissen@griffith.edu.au.",
    "Department of Biotechnology, College of Life Sciences & Biotechnology, Korea University, Seoul, 02841, Republic of Korea. Electronic address: chahong@korea.ac.kr."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Byeongmin Shin"
    },
    {
      "affs": [
        1
      ],
      "name": "Hye-Jin Kim Hawkes"
    },
    {
      "affs": [
        0
      ],
      "name": "Seonha Park"
    },
    {
      "affs": [
        0
      ],
      "name": "Hosam Ki"
    },
    {
      "affs": [
        0
      ],
      "name": "Sulhee Kim"
    },
    {
      "affs": [
        2
      ],
      "name": "Fenil Shah"
    },
    {
      "affs": [
        2
      ],
      "name": "Giovanna Di Trapani"
    },
    {
      "affs": [
        3
      ],
      "name": "Kathryn F Tonissen"
    },
    {
      "affs": [
        4
      ],
      "name": "Kwang Yeon Hwang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/58x2prg6pr0f2.bib",
  "cited_by": 0,
  "doi": "10.1016/j.redox.2026.104436",
  "fulltext_url": "https://europepmc.org/articles/PMC13678007",
  "id": "58x2prg6pr0f2",
  "issns": [
    "2213-2317"
  ],
  "landing_url": "https://europepmc.org/article/MED/42860110",
  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Redox biology and oxidative stress"
    ]
  ],
  "openalex": "W7221361176",
  "pdf_url": "https://europepmc.org/articles/PMC13678007?pdf=render",
  "pmcid": "PMC13678007",
  "pmid": "42860110",
  "published": "2026-10-10",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/58x2prg6pr0f2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:00Z",
      "native_id": "MED:42860110",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42860110"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Redox biology and oxidative stress",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Structural basis for cysteine-linked redox-state plasticity in mammalian methionine sulfoxide reductase A.",
  "title_text": "Structural basis for cysteine-linked redox-state plasticity in mammalian methionine sulfoxide reductase A.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:00Z",
  "url": "https://research.draconitic.com/paper/58x2prg6pr0f2",
  "venue": "Redox biology",
  "versions": []
}