ArticleAntimicrobial agents and chemotherapy2016
Nicotiana alata Defensin Chimeras Reveal Differences in the Mechanism of Fungal and Tumor Cell Killing and an Enhanced Antifungal Variant.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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29 citing papers in PubMed, 46 citations in OpenAlex.
- Anticandidal Activity and Low Cytotoxicity of Modified Analogues of the Tobacco Defensin NaD1.Antibiotics (Basel, Switzerland) · 2025Article
- Expression of a novel NaD1 recombinant antimicrobial peptide enhances antifungal and insecticidal activities.Scientific reports · 2024Article
- Antifungal Plant Defensins as an Alternative Tool to Combat Candidiasis.Plants (Basel, Switzerland) · 2024Review
- Modes of action and potential as a peptide-based biofungicide of a plant defensin MtDef4.Molecular plant pathology · 2024Article
- Fighting pathogenic yeasts with plant defensins and anti-fungal proteins from fungi.Applied microbiology and biotechnology · 2024Review
- Hyperpolarisation of Mitochondrial Membranes Is a Critical Component of the Antifungal Mechanism of the Plant Defensin, Ppdef1.Journal of fungi (Basel, Switzerland) · 2024Article
- The Plant Defensin Ppdef1 Is a Novel Topical Treatment for Onychomycosis.Journal of fungi (Basel, Switzerland) · 2023Article
- Prediction of global potential suitable habitats of Nicotiana alata Link et Otto based on MaxEnt model.Scientific reports · 2023Article
- Novel insights into plant defensin ingestion induced metabolic responses in the polyphagous insect pest Helicoverpa armigera.Scientific reports · 2023Article
- Use of Defensins to Develop Eco-Friendly Alternatives to Synthetic Fungicides to Control Phytopathogenic Fungi and Their Mycotoxins.Journal of fungi (Basel, Switzerland) · 2022Review
- Development of a FungalBraid Penicillium expansum-based expression system for the production of antifungal proteins in fungal biofactories.Microbial biotechnology · 2022Article
- Article
- Short Peptides Make a Big Difference: The Role of Botany-Derived AMPs in Disease Control and Protection of Human Health.International journal of molecular sciences · 2021Review
- Membrane-Interacting Antifungal Peptides.Frontiers in cell and developmental biology · 2021Review
- Peptides Derived From the α-Core and γ-Core Regions of a PutativeFrontiers in microbiology · 2021Article
- Histidine-Rich Defensins from theJournal of fungi (Basel, Switzerland) · 2020Article
- Modulation of Lymphocyte Potassium Channel KACS pharmacology & translational science · 2020Article
- Plant Defensins from a Structural Perspective.International journal of molecular sciences · 2020Review
- Inhibitory Activity of a Scorpion Defensin BmKDfsin3 against Hepatitis C Virus.Antibiotics (Basel, Switzerland) · 2020Article
- Improving the Digestibility of Plant Defensins to Meet Regulatory Requirements for Transgene Products in Crop Protection.Frontiers in plant science · 2020Article
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10 authors at 2 institutions in 1 country.
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Abstract
The plant defensin NaD1 is a potent antifungal molecule that also targets tumor cells with a high efficiency. We examined the features of NaD1 that contribute to these two activities by producing a series of chimeras with NaD2, a defensin that has relatively poor activity against fungi and no activity against tumor cells. All plant defensins have a common tertiary structure known as a cysteine-stabilized α-β motif which consists of an α helix and a triple-stranded β-sheet stabilized by four disulfide bonds. The chimeras were produced by replacing loops 1 to 7, the sequences between each of the conserved cysteine residues on NaD1, with the corresponding loops from NaD2. The loop 5 swap replaced the sequence motif (SKILRR) that mediates tight binding with phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and is essential for the potent cytotoxic effect of NaD1 on tumor cells. Consistent with previous reports, there was a strong correlation between PI(4,5)P2 binding and the tumor cell killing activity of all of the chimeras. However, this correlation did not extend to antifungal activity. Some of the loop swap chimeras were efficient antifungal molecules, even though they bound poorly to PI(4,5)P2, suggesting that additional mechanisms operate against fungal cells. Unexpectedly, the loop 1B swap chimera was 10 times more active than NaD1 against filamentous fungi. This led to the conclusion that defensin loops have evolved as modular components that combine to make antifungal molecules with variable mechanisms of action and that artificial combinations of loops can increase antifungal activity compared to that of the natural variants.
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