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


ABSTRACT: Acinetobacter baumannii 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 (k obs, 0.001 s-1) 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 (k obs, 0.02 s-1) and oxazole pre-Acb-Fe (ox-pre-Acb-Fe) (k obs, 0.08 s-1), 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 Shewanella SIPs. The biochemical and structural data presented here validate the role of BauF in A. baumannii iron assimilation and provide information important for drug design.

SUBMITTER: Valentino H 

PROVIDER: S-EPMC8296543 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Structural and Biochemical Characterization of the Flavin-Dependent Siderophore-Interacting Protein from <i>Acinetobacter baumannii</i>.

Valentino Hannah H   Korasick David A DA   Bohac Tabbetha J TJ   Shapiro Justin A JA   Wencewicz Timothy A TA   Tanner John J JJ   Sobrado Pablo P  

ACS omega 20210706 28


<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-fl  ...[more]

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