{
  "abstract": "The Gram-negative bacterium Burkholderia pseudomallei causes the severe disease melioidosis. β-Lactams, including carbapenems, are the primary treatment for B. pseudomallei infections, but are susceptible to chromosomal serine β-lactamases (SBLs), including the class D enzyme OXA-57. Here we show that recombinant OXA-57 is active toward penicillins and first-generation cephalosporins, slowly hydrolyzes carbapenems, including imipenem and meropenem, but is inactive toward oxyimino-cephalosporins (e.g., ceftazidime). Unlike many OXA enzymes, OXA-57 is sensitive to the mechanism-based SBL inhibitor clavulanic acid, but less so to the diazabicyclooctane avibactam and not to the cyclic boronate vaborbactam. Crystal structures of covalent OXA-57:avibactam and OXA-57:meropenem complexes reveal limited hydrogen-bonding interactions with bound ligands. In molecular dynamics simulations, the bound meropenem acyl-enzyme is mobile, with the 6α-hydroxyethyl group able to sample different orientations, while the water molecule necessary for deacylation is bound only transiently. These observations are consistent with the low level of meropenem turnover, supporting proposals that limited carbapenemase activity is a general property of OXA β-lactamases, and highlight the potential importance of OXA-57 in B. pseudomallei β-lactam resistance.",
  "abstract_shown": true,
  "affiliations": [
    "School of Biochemistry and Biomedical Sciences, University of Bristol, Bristol BS8 1TD, U.K.",
    "Diamond Light Source, Harwell Science and Innovation Campus, Didcot OX11 0DE, U.K.",
    "Centre for Computational Chemistry, School of Chemistry, University of Bristol, Bristol BS8 1TS, U.K.",
    "Chemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, Oxford OX1 3TA, U.K.",
    "Department of Life Sciences, University of Bath, Bath BA2 7AY, U.K.",
    "Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand",
    "Department of Medical Science, Mahidol University, Amnat Charoen Campus, Amnat Charoen 37000, Thailand",
    "Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand",
    "The Academy of Science, The Royal Society of Thailand, Bangkok 10300, Thailand"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Éilís C. Bragginton"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Charlotte K. Colenso"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Michael Beer",
      "orcid": "0000-0002-3879-3339"
    },
    {
      "affs": [
        3
      ],
      "name": "Karina Calvopiña"
    },
    {
      "affs": [
        0
      ],
      "name": "Philip Hinchliffe",
      "orcid": "0000-0001-8611-4743"
    },
    {
      "affs": [
        0
      ],
      "name": "John M. Shaw",
      "orcid": "0000-0001-9982-6096"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Catherine. L. Tooke"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Rathanin Seng"
    },
    {
      "affs": [
        5,
        7,
        8
      ],
      "name": "Narisara Chantratita"
    },
    {
      "affs": [
        2
      ],
      "name": "Adrian J. Mulholland",
      "orcid": "0000-0003-1015-4567"
    },
    {
      "affs": [
        3
      ],
      "name": "Christopher J. Schofield",
      "orcid": "0000-0002-0290-6565"
    },
    {
      "affs": [
        0
      ],
      "name": "James Spencer",
      "orcid": "0000-0002-4602-0571"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/brzabt5npt37r.bib",
  "cited_by": 3,
  "doi": "10.1021/acs.biochem.6c00668",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13738345/",
  "id": "brzabt5npt37r",
  "issns": [
    "0006-2960",
    "1520-4995"
  ],
  "landing_url": "https://doi.org/10.1021/acs.biochem.6c00668",
  "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",
      "Article"
    ],
    [
      "openalex",
      "2726|Antibiotic Resistance in Bacteria"
    ]
  ],
  "openalex": "W7223215896",
  "pdf_url": "https://pubs.acs.org/bichaw/article-pdf/doi/10.1021/acs.biochem.6c00668/68951014/acs.biochem.6c00668.pdf",
  "pmcid": "PMC13738345",
  "pmid": "42975168",
  "published": "2026-10-22",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/brzabt5npt37r.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:23:20Z",
      "native_id": "PMC13738345",
      "source": "pmc",
      "url": "https://doi.org/10.1021/acs.biochem.6c00668"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2726|Antibiotic Resistance in Bacteria",
      "subfield": "infectious-disease"
    }
  ],
  "title": "Structure and Dynamics of Burkholderia pseudomallei OXA-57, a Distinctive Low-Efficiency Class D β‑Lactamase with Carbapenem-Hydrolyzing Activity",
  "title_text": "Structure and Dynamics of Burkholderia pseudomallei OXA-57, a Distinctive Low-Efficiency Class D β‑Lactamase with Carbapenem-Hydrolyzing Activity",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:23:20Z",
  "url": "https://research.draconitic.com/paper/brzabt5npt37r",
  "venue": "Biochemistry",
  "versions": []
}