# Histatin 8 Interactions with Copper, Zinc, and Nickel Ions, and Its Antimicrobial Profile in Relation to Histatin 5

## TL;DR

This study compares the metal ion binding and antimicrobial properties of histatin 8 and histatin 5, revealing differences in copper and zinc interactions that may affect their antifungal activity.

## Contribution

The study reveals distinct metal-binding profiles of Hst8 compared to Hst5, offering new insights into how metal coordination influences histatin antimicrobial activity.

## Key findings

- Hst8 interacts with Cu(II), Zn(II), and Ni(II) ions, but shows distinct binding characteristics compared to Hst5.
- Hst5 has two copper-binding sites with different dissociation constants, while Hst8 has only one.
- The antimicrobial activity of Hst5 and Hst8 varies against different microbial strains.

## Abstract

Histatins are histidine-rich antimicrobial peptides present in human saliva, with histatin 5 (Hst5) demonstrating the most potent antifungal activity. Previous studies have linked the antifungal properties of histatins, particularly those against Candida species, to their ability to bind metal ions such as Cu(II) and Zn(II). While the antimicrobial activity of some histatins is well established, the impact of metal ion coordination on this activity remains an area of ongoing investigation. This study focuses on histatin 8 (Hst8), a less-explored member of the histatin family, and compares its metal-binding and antimicrobial properties to those of Hst5. Using isothermal titration microcalorimetry (ITC), we examined the interactions of Hst8 with Cu(II), Zn(II), and Ni(II) ions and evaluated its antimicrobial activity against Escherichia coli, Staphylococcus aureus and two Candida albicans strains. Our findings revealed significant differences in copper and zinc binding between Hst5 and Hst8, with both peptides exhibiting distinct antifungal profiles. Interestingly, it has been shown that copper ions bind to Hst5 in a distinctly different manner than to Hst8. Hst5 exhibits two binding sites with dissociation constants (KDITC) of 0.2 µM and 14.8 µM, whereas Hst8 has only one set of binding sites with a KDITC of 12.3 µM. These results highlight the potential role of metal ion coordination in modulating the antimicrobial efficacy of histatins, providing further insight into their therapeutic potential.