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The mycobacterial ABC transporter IrtAB employs a membrane-facing crevice for siderophore-mediated iron uptake.
Nat Commun
January 2025
Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland.
The mycobacterial ABC transporter IrtAB features an ABC exporter fold, yet it imports iron-charged siderophores called mycobactins. Here, we present extensive cryo-EM analyses and DEER measurements, revealing that IrtAB alternates between an inward-facing and an outward-occluded conformation, but does not sample an outward-facing conformation. When IrtAB is locked in its outward-occluded conformation in nanodiscs, mycobactin is bound in the middle of the lipid bilayer at a membrane-facing crevice opening at the heterodimeric interface.
View Article and Find Full Text PDFIron-associated lipid peroxidation in Alzheimer's disease is increased in lipid rafts with decreased ferroptosis suppressors, tested by chelation in mice.
Alzheimers Dement
January 2025
Leonard Davis School of Gerontology, University of Southern California, Los Angeles, California, USA.
Introduction: Iron-mediated cell death (ferroptosis) is a proposed mechanism of Alzheimer's disease (AD) pathology. While iron is essential for basic biological functions, its reactivity generates oxidants which contribute to cell damage and death.
Methods: To further resolve mechanisms of iron-mediated toxicity in AD, we analyzed post mortem human brain and ApoEFAD mice.
Isolation and Bioactivity of Natural Products from sp. MA37.
Molecules
January 2025
Marine Biodiscovery Centre, Department of Chemistry, School of Natural and Computing Sciences, University of Aberdeen, Old Aberdeen AB24 3UE, UK.
The isolation and characterization of bioactive metabolites from species continue to represent a vital area of research, given their potential in natural product drug discovery. In this study, we characterize a new siderophore called legonoxamine I, together with a known compound, streptimidone, from the talented soil bacterium sp. MA37, using chromatographic techniques and spectroscopic analysis.
View Article and Find Full Text PDFChemical Logic of Peptide Branching by Iterative Nonlinear Nonribosomal Peptide Synthetases.
Biochemistry
January 2025
Department of Chemistry, Washington University in St. Louis, One Brookings Drive, St. Louis, Missouri 63130, United States.
Branch-point syntheses in nonribosomal peptide assembly are rare but useful strategies to generate tripodal peptides with advantageous hexadentate iron-chelating capabilities, as seen in siderophores. However, the chemical logic underlying the peptide branching by nonribosomal peptide synthetase (NRPS) often remains complex and elusive. Here, we review the common strategies for the biosynthesis of branched nonribosomal peptides (NRPs) and present our biochemical investigation on the NRPS-catalyzed assembly of fimsbactin A, a branched mixed-ligand siderophore produced by the human pathogenic strain .
View Article and Find Full Text PDFSidF, a dual substrate N5-acetyl-N5-hydroxy-L-ornithine transacetylase involved in siderophore biosynthesis.
J Struct Biol X
June 2025
Bioorganic Chemistry and Bio-Crystallography Laboratory (B2Cl) Faculty of Agricultural, Environmental and Food Sciences, Libera Università di Bolzano, Piazza Università, 1, 39100 Bolzano, Italy.
Siderophore-mediated iron acquisition is essential for the virulence of , a fungus causing life-threatening aspergillosis. Drugs targeting the siderophore biosynthetic pathway could help improve disease management. The transacetylases SidF and SidL generate intermediates for different siderophores in .
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