1. Vaccatides: Antifungal Glutamine-Rich Hevein-Like Peptides from Vaccaria hispanica
- Author
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Wei Liang Tan, Siu Kwan Sze, Aida Serra, Tianshu Xiao, Shruthi G. Kini, James P. Tam, Ka Ho Wong, and School of Biological Sciences
- Subjects
0301 basic medicine ,hevein-like peptides ,Caryophyllaceae ,Vaccaria hispanica ,Sequence (biology) ,Plant Science ,lcsh:Plant culture ,hevein ,03 medical and health sciences ,chemistry.chemical_compound ,Biosynthesis ,lcsh:SB1-1110 ,Mycelium ,Original Research ,anti-fungal ,chemistry.chemical_classification ,Hevein-like Peptides ,030102 biochemistry & molecular biology ,biology ,Cystine knot ,biology.organism_classification ,Amino acid ,Glutamine ,030104 developmental biology ,Biochemistry ,chemistry ,Vaccaria Hispanica ,cysteine-rich peptides ,Cysteine - Abstract
Hevein and hevein-like peptides are disulfide-constrained chitin-binding cysteine-rich peptides. They are divided into three subfamilies, 6C-, 8C-, and 10C-hevein-like peptides, based on the number of cysteine residues. In addition, hevein-like peptides can exist in two forms, short and long. The long C-terminal form found in hevein and 10C-hevein-like peptides contain a C-terminal protein cargo. In contrast, the short form without a protein cargo is found in all three subfamilies. Here, we report the discovery and characterization of two novel glutamine-rich and protein cargo-free 8C-hevein-like peptides, vaccatides vH1 and vH2, from Vaccaria hispanica of the Caryophyllaceae family. Proteomic analyses showed that the vaccatides are 40–41 amino acids in length and contain a chitin-binding domain. NMR determination revealed that vaccatide vH2 displays a highly compact structure with a N-terminal cystine knot and an addition C-terminal disulfide bond. Stability studies showed that this compact structure renders vaccatide vH2 resistant to thermal, chemical and proteolytic degradation. The chitin-binding vH2 was shown to inhibit the mycelium growth of four phyto-pathogenic fungal strains with IC50 values in the micromolar range. Our findings show that vaccatides represent a new family of 8C-hevein-like peptides, which are protein cargo-free and glutamine-rich, characteristics that differentiate them from the prototypic hevein and the 10C-hevein-like peptides. In summary, this study enriches the existing library of hevein-like peptides and provides insight into their molecular diversity in sequence, structure and biosynthesis. Additionally, their highly disulfide-constrained structure could be used as a scaffold for developing metabolically and orally active peptidyl therapeutics. NRF (Natl Research Foundation, S’pore) Published version
- Published
- 2017