{Reference Type}: Journal Article
{Title}: The second N-terminal aromatic residue of the fungal defensin, blapersin, of Blastomyces percursus is essential for its antibacterial activity.
{Author}: Wu J;Qu C;Zhang S;Chen W;Wang S;
{Journal}: Peptides
{Volume}: 133
{Issue}: 0
{Year}: 11 2020
{Factor}: 3.867
{DOI}: 10.1016/j.peptides.2020.170400
{Abstract}: Studies have shown that the second N-terminal residue of fungal defensins is closely involved in the binding of defensins to lipid II, a bacterial cell wall precursor, and plays an important role in antibacterial activity. We found that the N-terminal residue is always aromatic in nature. In this study, 29 fungal defensin-like peptides were found via the genomic search strategy. Based on the type of aromatic residue at the second N-terminal site, we mainly divided these peptides into Phe, Trp, and Tyr types. We selected and characterized a defensin, blapersin, derived from Blastomyces percursus as a molecular model to investigate the functional significance of the N-terminal site. The native blapersin killed a wide spectrum of gram-positive bacteria at low molecular concentrations. Its aromatic mutants, W2F and W2Y, displayed enhanced antimicrobial activity, especially against the vancomycin-resistant Enterococcus faecium. The aromatic side chains containing Phe2 and Tyr2 seem to be more favorable for the antibacterial activity of blapersin those containing Trp2. However, the nonaromatic mutant W2A had almost no antibacterial activity. This indicates that the second N-terminal aromatic residue is essential for the antimicrobial action of blapersin. All these defensins have high stability and low toxicity. This is the first report on the enhancement of antibacterial activity by calibration of the N-terminal aromatic residue.