{
  "abstract": "Chondroitin sulfate (CS) and dermatan sulfate (DS) are glycosaminoglycans whose diverse biological functions are largely determined by specific sulfation patterns. The GlcA/IdoA-GalNAc4S (A/iA unit), where GlcA, IdoA, GalNAc and 4S denote D-glucuronic acid, L-iduronic acid, GalNAc, and 4-O-sulfation, respectively, is the most prevalent sulfation motif in animal tissues and participates in a broad spectrum of physiological and pathological processes. However, chondroitinase A (CSase A), a lyase capable of selectively degrading CS/DS rich in A/iA units, has not yet been identified, which has limited our understanding of the functional roles of such structures in CS/DS. Here, we report the first discovery of a CSase A from the metagenome of sediments near the Haima cold seep. This enzyme belongs to polysaccharide lyase family 8 and exhibits strict selectivity for A/iA units, yielding disaccharides composed almost exclusively of the 4-O-sulfated disaccharide, with no other sulfated disaccharide variants detectable even under exhaustive digestion. Structural analysis of resistant tetrasaccharides and hexasaccharides, and degradation assays with structure-defined oligosaccharides demonstrate that CSase A exclusively cleaves the β-1,4 glycosidic bond preceding a disaccharide unit containing GalNAc or GalNAc4S, thereby defining its rigorous substrate specificity. Site-directed mutagenesis and activity profiling identified Glu-579, Arg-480, Tyr-427, and His-420 as residues essential for catalysis, supporting a proposed tyrosine-histidine-mediated acid-base mechanism. The discovery of CSase A provides a unique molecular tool for dissecting the functional roles of A/iA units in CS/DS-related biology and disease.",
  "abstract_shown": true,
  "affiliations": [
    "National Glycoengineering Research Center, State Key Laboratory of Microbial Technology, Shandong Center of Technology Innovation for Carbohydrate, Shandong Key Laboratory of Carbohydrate and Carbohydrate-conjugate Drugs, Shandong University, Qingdao, People's Republic of China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Wenshuang Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Haixin Yi"
    },
    {
      "affs": [
        0
      ],
      "name": "Ping’en Zi"
    },
    {
      "affs": [
        0
      ],
      "name": "Xu Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Rouyi Zou"
    },
    {
      "affs": [
        0
      ],
      "name": "Yu-zhong Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Fuchuan Li"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bfg5rvyt8fk4t.bib",
  "cited_by": 0,
  "doi": "10.1016/j.jbc.2026.113594",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13696812/",
  "id": "bfg5rvyt8fk4t",
  "issns": [
    "0021-9258",
    "1083-351X"
  ],
  "landing_url": "https://doi.org/10.1016/j.jbc.2026.113594",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article Collection: Glycobiology and Extracellular Matrices"
    ],
    [
      "openalex",
      "1307|Proteoglycans and glycosaminoglycans research"
    ]
  ],
  "openalex": "W7214026525",
  "pdf_url": null,
  "pmcid": "PMC13696812",
  "pmid": "42772565",
  "published": "2026-09-22",
  "publisher": "American Society for Biochemistry and Molecular Biology",
  "ris": "https://research.draconitic.com/paper/bfg5rvyt8fk4t.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:06Z",
      "native_id": "PMC13696812",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.jbc.2026.113594"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1307|Proteoglycans and glycosaminoglycans research",
      "subfield": "cell-biology"
    }
  ],
  "title": "Discovery and characterization of chondroitinase A with specificity for 4-O-sulfated GalNAc in chondroitin sulfate/dermatan sulfate",
  "title_text": "Discovery and characterization of chondroitinase A with specificity for 4-O-sulfated GalNAc in chondroitin sulfate/dermatan sulfate",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:34:05Z",
  "url": "https://research.draconitic.com/paper/bfg5rvyt8fk4t",
  "venue": "The Journal of Biological Chemistry",
  "versions": []
}