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Structure of the Siderophore Interacting Protein from Acinetbacter baumanniiStructure of the Siderophore Interacting Protein from Acinetbacter baumannii
Structural highlights
FunctionPublication Abstract from PubMedAcinetobacter 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 A 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. Structural and Biochemical Characterization of the Flavin-Dependent Siderophore-Interacting Protein from Acinetobacter baumannii.,Valentino H, Korasick DA, Bohac TJ, Shapiro JA, Wencewicz TA, Tanner JJ, Sobrado P ACS Omega. 2021 Jul 6;6(28):18537-18547. doi: 10.1021/acsomega.1c03047., eCollection 2021 Jul 20. PMID:34308084[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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