Spectroscopic investigations on fungal aspartic protease as target of gallic acid

Proteases are a major virulence factor in pathogenic fungi and can serve as a potential therapeutic target. The interaction of gallic acid (GA) with Aspartic fungal protease (PepA) was investigated using biophysical and in silico approaches. UV-Vis and fluorescence spectroscopy showed complex formation and static quenching of PepA by GA with Ka of 7.4 x 105 M-1 and stoichiometric binding site (n) of 1.67. CD-spectroscopy showed marked changes in helical content and synchronous fluorescence spectra measurements indicated significant changes in the microenvironment around tryptophan residues in the GA-PepA complex. Outcomes of Isothermal Titration Calorimetry (ITC) measurement and molecular modelling studies validated the spectroscopic results. The binding of GA to Human Serum albumin (HSA) was moderate (Ka = 1.9 x 103 M-1) and did not cause structural disruption of HSA. To conclude, gallic acid is strongly bound to fungal protease leading to structural disruption and inhibition whereas HSA structure was largely conserved. Gallic acid thus appears to be a potential therapeutic agent against fungal proteases.

Automated summary

In this study, the interaction between gallic acid (GA) and Aspartic fungal protease (PepA) was investigated using biophysical and in silico approaches. The results showed that GA strongly binds to PepA, leading to structural disruption and inhibition of its activity. However, the binding of GA to Human Serum albumin (HSA) was moderate and did not cause structural disruption.