ArticleScientific reports2019
Specific metallo-protein interactions and antimicrobial activity in Histatin-5, an intrinsically disordered salivary peptide.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Non-specific Protein and Peptide Antibacterial Factors of Mammals.The protein journal · 2026Review
- Protective effect of histatin 5 and amphotericin B conjugated nanostructures in C. albicans challenged Swiss albino mice.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Structural information in therapeutic peptides: Emerging applications in biomedicine.FEBS open bio · 2025Review
- The limits of prediction: Why intrinsically disordered regions challenge our understanding of antimicrobial peptides.Computational and structural biotechnology journal · 2024Article
- Capping motifs in antimicrobial peptides and their relevance for improved biological activities.Frontiers in chemistry · 2024Review
- Histatin-5 interacts with cellular copper to promote antifungal activity against Candida albicans.Metallomics : integrated biometal science · 2023Article
- The Synergy between Zinc and Antimicrobial Peptides: An Insight into Unique Bioinorganic Interactions.Molecules (Basel, Switzerland) · 2023Review
- Zinc Binding Inhibits Cellular Uptake and Antifungal Activity of Histatin-5 inACS infectious diseases · 2022Article
- Antimicrobial Peptides with Anti-International journal of molecular sciences · 2022Review
- Alternative Antibiotics in Dentistry: Antimicrobial Peptides.Pharmaceutics · 2022Review
- A Novel Role for Histatin 5 in Combination with Zinc to Promote Commensalism inPathogens (Basel, Switzerland) · 2021Article
- Histatin 5 Metallopeptides and Their Potential againstBiomolecules · 2021Review
- Folding and self-assembly of short intrinsically disordered peptides and protein regions.Nanoscale advances · 2021Review
- Membrane-Interacting Antifungal Peptides.Frontiers in cell and developmental biology · 2021Review
- Designed Metal-ATCUN Derivatives: Redox- and Non-redox-Based Applications Relevant for Chemistry, Biology, and Medicine.iScience · 2020Review
- Concentration- and pH-Dependent Oligomerization of the Thrombin-Derived C-Terminal Peptide TCP-25.Biomolecules · 2020Article
- Histidine-Rich Defensins from theJournal of fungi (Basel, Switzerland) · 2020Article
- Zinc Binding by Histatin 5 Promotes Fungicidal Membrane Disruption inJournal of fungi (Basel, Switzerland) · 2020Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Histatin-5 (Hst-5) is an antimicrobial, salivary protein that is involved in the host defense system. Hst-5 has been proposed to bind functionally relevant zinc and copper but presents challenges in structural studies due to its disordered conformation in aqueous solution. Here, we used circular dichroism (CD) and UV resonance Raman (UVRR) spectroscopy to define metallo-Hst-5 interactions in aqueous solution. A zinc-containing Hst-5 sample exhibits shifted Raman bands, relative to bands observed in the absence of zinc. Based on comparison to model compounds and to a family of designed, zinc-binding beta hairpins, the alterations in the Hst-5 UVRR spectrum are attributed to zinc coordination by imidazole side chains. Zinc addition also shifted a tyrosine aromatic ring UVRR band through an electrostatic interaction. Copper addition did not have these effects. A sequence variant, H18A/H19A, was employed; this mutant has less potent antifungal activity, when compared to Hst-5. Zinc addition had only a small effect on the thermal stability of this mutant. Interestingly, both zinc and copper addition shifted histidine UVRR bands in a manner diagnostic for metal coordination. Results obtained with a K13E/R22G mutant were similar to those obtained with wildtype. These experiments show that H18 and H19 contribute to a zinc binding site. In the H18A/H19A mutant the specificity of the copper/zinc binding sites is lost. The experiments implicate specific zinc binding to be important in the antimicrobial activity of Hst-5.
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