Structural and Biochemical Characterization of the Flavin-Dependent Siderophore-Interacting Protein from Acinetobacter baumannii

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dc.contributor.authorValentino, Hannahen
dc.contributor.authorKorasick, David A.en
dc.contributor.authorBohac, Tabbetha J.en
dc.contributor.authorShapiro, Justin A.en
dc.contributor.authorWencewicz, Timothy A.en
dc.contributor.authorTanner, John J.en
dc.contributor.authorSobrado, Pabloen
dc.contributor.departmentBiochemistryen
dc.date.accessioned2021-08-04T19:09:48Zen
dc.date.available2021-08-04T19:09:48Zen
dc.date.issued2021-07-06en
dc.date.updated2021-08-04T19:09:24Zen
dc.description.abstract<i>Acinetobacter baumannii</i> is an opportunistic pathogen with a high mortality rate due to multi-drug-resistant strains. The synthesis and uptake of the iron-chelating siderophores acinetobactin (Acb) and preacinetobactin (pre-Acb) have been shown to be essential for virulence. Here, we report the kinetic and structural characterization of BauF, a flavin-dependent siderophore-interacting protein (SIP) required for the reduction of Fe(III) bound to Acb/pre-Acb and release of Fe(II). Stopped-flow spectrophotometric studies of the reductive half-reaction show that BauF forms a stable neutral flavin semiquinone intermediate. Reduction with NAD(P)H is very slow (<i>k</i> <sub>obs</sub>, 0.001 s<sup>-1</sup>) and commensurate with the rate of reduction by photobleaching, suggesting that NAD(P)H are not the physiological partners of BauF. The reduced BauF was oxidized by Acb-Fe (<i>k</i> <sub>obs</sub>, 0.02 s<sup>-1</sup>) and oxazole pre-Acb-Fe (ox-pre-Acb-Fe) (<i>k</i> <sub>obs</sub>, 0.08 s<sup>-1</sup>), a rigid analogue of pre-Acb, at a rate 3-11 times faster than that with molecular oxygen alone. The structure of FAD-bound BauF was solved at 2.85 Å and was found to share a similarity to <i>Shewanella</i> SIPs. The biochemical and structural data presented here validate the role of BauF in <i>A. baumannii</i> iron assimilation and provide information important for drug design.en
dc.description.versionPublished versionen
dc.format.extentPages 18537-18547en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1021/acsomega.1c03047en
dc.identifier.eissn2470-1343en
dc.identifier.issn2470-1343en
dc.identifier.issue28en
dc.identifier.orcidSobrado, Pablo [0000-0003-1494-5382]en
dc.identifier.otherPMC8296543 (pmc)en
dc.identifier.pmid34308084 (pubmed)en
dc.identifier.urihttp://hdl.handle.net/10919/104576en
dc.identifier.volume6en
dc.language.isoenen
dc.publisherAmerican Chemical Societyen
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/34308084en
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subject0904 Chemical Engineeringen
dc.subject0912 Materials Engineeringen
dc.titleStructural and Biochemical Characterization of the Flavin-Dependent Siderophore-Interacting Protein from <i>Acinetobacter baumannii</i>en
dc.title.serialACS Omegaen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherresearch-articleen
dc.type.otherJournal Articleen
dcterms.dateAccepted2021-06-23en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciencesen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/Biochemistryen
pubs.organisational-group/Virginia Tech/University Research Institutesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciencesen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/CALS T&R Facultyen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciences/Durelle Scotten

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