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In Gram\u2010negative species, these bonds are introduced by the Dsb enzyme family, with DsbA acting as the primary thiol oxidase. While DsbA proteins share a conserved thioredoxin (TRX)\u2010like fold, emerging evidence highlights substantial structural and functional divergence among pathogenic homologues. Here, we present the high\u2010resolution crystal structure and functional characterization of BperDsbA, a DsbA homologue from\n                    <jats:italic>Bordetella pertussis<\/jats:italic>\n                    , the causative agent of whooping cough. BperDsbA adopts a canonical TRX fold with a CPHC active site and a threonine\u2010containing cis\u2010proline loop, but displays striking deviations from prototypical DsbAs. Notably, it contains a highly destabilizing catalytic Dsb, resulting in one of the most oxidizing redox potentials recorded for a DsbA enzyme. Surface electrostatic analysis reveals an unusual distribution of positive and negative charge around the active site, in contrast to the broadly hydrophobic catalytic surfaces of other DsbAs. Functionally, BperDsbA shows limited substrate promiscuity and selectively catalyzes the oxidative folding of a pertussis toxin\u2010derived peptide, supporting a model of substrate specialization. Together, these findings suggest that BperDsbA has evolved unique redox and structural features to support virulence factor maturation in\n                    <jats:italic>B. pertussis<\/jats:italic>\n                    . This work expands our understanding of the mechanistic diversity of DsbA enzymes and highlights their potential as pathogen\u2010specific targets for anti\u2010virulence therapeutics.\n                  <\/jats:p>","DOI":"10.1002\/pro.70421","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T13:27:07Z","timestamp":1766496427000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Structural and functional specialization of\n                    <i>Bordetella pertussis<\/i>\n                    <scp>DsbA<\/scp>\n                    for pertussis toxin folding"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6223-0153","authenticated-orcid":false,"given":"Stephanie","family":"Penning","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, School of Agriculture Biomedicine and 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