Show simple item record

dc.contributor.authorSubedi, Pramod
dc.contributor.authorPaxman, Jason J
dc.contributor.authorWang, Geqing
dc.contributor.authorHor, Lilian
dc.contributor.authorHong, Yaoqin
dc.contributor.authorVerderosa, Anthony D
dc.contributor.authorWhitten, Andrew E
dc.contributor.authorPanjikar, Santosh
dc.contributor.authorSantos-Martin, Carlos F
dc.contributor.authorMartin, Jennifer L
dc.contributor.authorTotsika, Makrina
dc.contributor.authorHeras, Begoña
dc.date.accessioned2021-05-18T23:57:26Z
dc.date.available2021-05-18T23:57:26Z
dc.date.issued2021
dc.identifier.issn1523-0864
dc.identifier.doi10.1089/ars.2020.8218
dc.identifier.urihttp://hdl.handle.net/10072/404490
dc.description.abstractAims: Thioredoxin (TRX)-fold proteins are ubiquitous in nature. This redox scaffold has evolved to enable a variety of functions, including redox regulation, protein folding, and oxidative stress defense. In bacteria, the TRX-like disulfide bond (Dsb) family mediates the oxidative folding of multiple proteins required for fitness and pathogenic potential. Conventionally, Dsb proteins have specific redox functions with monomeric and dimeric Dsbs exclusively catalyzing thiol oxidation and disulfide isomerization, respectively. This contrasts with the eukaryotic disulfide forming machinery where the modular TRX protein disulfide isomerase (PDI) mediates thiol oxidation and disulfide reshuffling. In this study, we identified and structurally and biochemically characterized a novel Dsb-like protein from Salmonella enterica termed bovine colonization factor protein H (BcfH) and defined its role in virulence. Results: In the conserved bovine colonization factor (bcf) fimbrial operon, the Dsb-like enzyme BcfH forms a trimeric structure, exceptionally uncommon among the large and evolutionary conserved TRX superfamily. This protein also displays very unusual catalytic redox centers, including an unwound α-helix holding the redox active site and a trans-proline instead of the conserved cis-proline active site loop. Remarkably, BcfH displays both thiol oxidase and disulfide isomerase activities contributing to Salmonella fimbrial biogenesis. Innovation and Conclusion: Typically, oligomerization of bacterial Dsb proteins modulates their redox function, with monomeric and dimeric Dsbs mediating thiol oxidation and disulfide isomerization, respectively. This study demonstrates a further structural and functional malleability in the TRX-fold protein family. BcfH trimeric architecture and unconventional catalytic sites permit multiple redox functions emulating in bacteria the eukaryotic PDI dual oxidoreductase activity.
dc.description.peerreviewedYes
dc.languageeng
dc.publisherMary Ann Liebert Inc
dc.relation.ispartofissue1
dc.relation.ispartofjournalAntioxidants & Redox Signaling
dc.relation.ispartofvolume35
dc.subject.fieldofresearchBiochemistry and Cell Biology
dc.subject.fieldofresearchMedical Biochemistry and Metabolomics
dc.subject.fieldofresearchPharmacology and Pharmaceutical Sciences
dc.subject.fieldofresearchcode0601
dc.subject.fieldofresearchcode1101
dc.subject.fieldofresearchcode1115
dc.subject.keywordsDsb proteins
dc.subject.keywordsbacterial infection
dc.subject.keywordsbiofilm
dc.subject.keywordscolonization
dc.subject.keywordsdisulfide catalysis
dc.titleSalmonella enterica BcfH Is a Trimeric Thioredoxin-Like Bifunctional Enzyme with Both Thiol Oxidase and Disulfide Isomerase Activities
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationSubedi, P; Paxman, JJ; Wang, G; Hor, L; Hong, Y; Verderosa, AD; Whitten, AE; Panjikar, S; Santos-Martin, CF; Martin, JL; Totsika, M; Heras, B, Salmonella enterica BcfH Is a Trimeric Thioredoxin-Like Bifunctional Enzyme with Both Thiol Oxidase and Disulfide Isomerase Activities, Antioxidants & Redox Signaling, 2021, 35 (1)
dc.date.updated2021-05-18T21:31:45Z
gro.hasfulltextNo Full Text
gro.griffith.authorMartin, Jennifer


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

  • Journal articles
    Contains articles published by Griffith authors in scholarly journals.

Show simple item record