The structure of a novel ferredoxin – FhuF, a ferric-siderophore reductase from E. coli K-12 with a novel 2Fe-2S cluster coordination

Trindade, Inês B.; Rollo, Filipe; Todorović, Smilja; Catarino, Teresa; Moe, Elin; Matías, Pedro M.; Piccioli, Mario; Louro, Ricardo O.

doi:10.1101/2023.07.04.547673

Cited by 2 publications

(1 citation statement)

References 52 publications

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“…The sequence of SbFSR shows identities of 35 % to FhuF (Escherichia coli K-12) and 22 % to FchR (Alkalihalophilus pseudofirmus). It has an identical cluster binding motif sequence (C-C-x10-C-x2-C) and AlphaFold2, predicts overall folding conservation when compared to the archetypical FhuF from E. coli (29,30). However, SbFSR contains three extra α-helices and a longer N-terminal loop (Supplementary Information, Fig.…”

Section: Production Of Fe(iii)-siderophore Reductases Sbsip and Sbfsrmentioning

confidence: 99%

Flavin-containing siderophore-interacting protein ofShewanella putrefaciensDSM 9451 reveals substrate specificity in ferric-siderophore reduction

Trindade,

Fonseca,

Catarino

et al. 2024

Preprint

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Shewanella are bacteria widespread in marine and brackish water environments and emergent opportunistic pathogens. Their environmental versatility is highly dependent on the ability to produce an abundance of iron-rich proteins, mainly multiheme c-type cytochromes. Although iron plays a vital role in the ability of Shewanella species to survive in various environments, very few studies exist regarding the strategies by which these bacteria scavenge iron from the environment. Small molecule siderophore-mediated iron transport is a strategy commonly employed for iron acquisition, and it was identified amongst Shewanella spp. over two decades ago. Shewanella species produce hydroxamate-type siderophores and iron removal from these compounds can occur in the cytoplasm via Fe(III)-siderophore reduction mediated by siderophore-interacting proteins (SIPs). The genome of Shewanella putrefaciens DSM 9451 isolated from an infected child contains representatives of the two different cytosolic families of SIPs: the flavin-containing siderophore interacting protein family (SIP) and the iron−sulfur cluster-containing ferric siderophore reductase family (FSR). Here, we report the expression and purification of the flavin-containing (SbSIP) and iron-sulfur cluster-containing (SbFSR) Fe(III)-siderophore reductases of Shewanella putrefaciens DSM 9451. The structural and functional characterization of SbSIP shows distinct features from the highly homologous SIP from Shewanella frigidimarina (SfSIP). These include significant structural differences, different binding affinities for NADH and NADPH, and lower rates of Fe(III)-siderophore reduction, results which consolidate in the putative identification of the binding pocket for these proteins. Overall our work highlights NADH and NADPH specificity and the different Fe(III)-siderophore reduction abilities of the SIP family suggesting a tailoring of these enzymes towards meeting different microbial iron requirements.

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Section: Production Of Fe(iii)-siderophore Reductases Sbsip and Sbfsrmentioning

confidence: 99%

Flavin-containing siderophore-interacting protein ofShewanella putrefaciensDSM 9451 reveals substrate specificity in ferric-siderophore reduction

Trindade,

Fonseca,

Catarino

et al. 2024

Preprint

Self Cite

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Location, Location, Location: Establishing Design Principles for New Antibacterials from Ferric Siderophore Transport Systems

Luo,

Peczuh

2024

Molecules

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This review strives to assemble a set of molecular design principles that enables the delivery of antibiotic warheads to Gram-negative bacterial targets (ESKAPE pathogens) using iron-chelating siderophores, known as the Trojan Horse strategy for antibiotic development. Principles are derived along two main lines. First, archetypical siderophores and their conjugates are used as case studies for native iron transport. They enable the consideration of the correspondence of iron transport and antibacterial target location. The second line of study charts the rationale behind the clinical antibiotic cefiderocol. It illustrates the potential versatility for the design of new Trojan Horse-based antibiotics. Themes such as matching the warhead to a location where the siderophore delivers its cargo (i.e., periplasm vs. cytoplasm), whether or not a cleavable linker is required, and the relevance of cheaters to the effectiveness and selectivity of new conjugates will be explored. The effort to articulate rules has identified gaps in the current understanding of iron transport pathways and suggests directions for new investigations.

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The structure of a novel ferredoxin – FhuF, a ferric-siderophore reductase from E. coli K-12 with a novel 2Fe-2S cluster coordination

Cited by 2 publications

References 52 publications

Flavin-containing siderophore-interacting protein ofShewanella putrefaciensDSM 9451 reveals substrate specificity in ferric-siderophore reduction

Flavin-containing siderophore-interacting protein ofShewanella putrefaciensDSM 9451 reveals substrate specificity in ferric-siderophore reduction

Location, Location, Location: Establishing Design Principles for New Antibacterials from Ferric Siderophore Transport Systems

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