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Conjuring up a ghost: structural and functional characterization of FhuF, a ferric siderophore reductase from E. coli
- Source :
- Journal of Biological Inorganic Chemistry, Journal of Biological Inorganic Chemistry, 2021, 26 (2-3), pp.313-326. ⟨10.1007/s00775-021-01854-y⟩, Journal of Biological Inorganic Chemistry, Springer Verlag, 2021, ⟨10.1007/s00775-021-01854-y⟩, J Biol Inorg Chem
- Publication Year :
- 2021
- Publisher :
- Springer International Publishing, 2021.
-
Abstract
- Graphic abstract Iron is a fundamental element for virtually all forms of life. Despite its abundance, its bioavailability is limited, and thus, microbes developed siderophores, small molecules, which are synthesized inside the cell and then released outside for iron scavenging. Once inside the cell, iron removal does not occur spontaneously, instead this process is mediated by siderophore-interacting proteins (SIP) and/or by ferric-siderophore reductases (FSR). In the past two decades, representatives of the SIP subfamily have been structurally and biochemically characterized; however, the same was not achieved for the FSR subfamily. Here, we initiate the structural and functional characterization of FhuF, the first and only FSR ever isolated. FhuF is a globular monomeric protein mainly composed by α-helices sheltering internal cavities in a fold resembling the “palm” domain found in siderophore biosynthetic enzymes. Paramagnetic NMR spectroscopy revealed that the core of the cluster has electronic properties in line with those of previously characterized 2Fe–2S ferredoxins and differences appear to be confined to the coordination of Fe(III) in the reduced protein. In particular, the two cysteines coordinating this iron appear to have substantially different bond strengths. In similarity with the proteins from the SIP subfamily, FhuF binds both the iron-loaded and the apo forms of ferrichrome in the micromolar range and cyclic voltammetry reveals the presence of redox-Bohr effect, which broadens the range of ferric-siderophore substrates that can be thermodynamically accessible for reduction. This study suggests that despite the structural differences between FSR and SIP proteins, mechanistic similarities exist between the two classes of proteins. Supplementary Information The online version contains supplementary material available at 10.1007/s00775-021-01854-y.
- Subjects :
- 0301 basic medicine
Models, Molecular
Siderophore
Subfamily
FMN Reductase
Stereochemistry
Redox-Bohr effect
Reductase
Ferric-siderophore reductase
Biochemistry
2Fe–2S protein
Inorganic Chemistry
03 medical and health sciences
chemistry.chemical_compound
Protein Domains
medicine
Escherichia coli
[CHIM]Chemical Sciences
Cysteine
Ferredoxin
Ferrichrome
Original Paper
030102 biochemistry & molecular biology
Chemistry
Nuclear magnetic resonance spectroscopy
Iron uptake
Small molecule
030104 developmental biology
Ferric
Oxidation-Reduction
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 14321327 and 09498257
- Volume :
- 26
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Inorganic Chemistry
- Accession number :
- edsair.doi.dedup.....d1e06fe4321cbd6185fba9f52d868b4e