Introduction:
Lactoperoxidase (LPO) is a member of mammalian heme peroxidase family and is an enzyme of innate
immune system. It possesses a covalently linked heme prosthetic group (a derivative of protoporphyrin IX) in its active
site. LPO catalyzes the oxidation of halides and pseudohalides in the presence of hydrogen peroxide (H2O2) and shows a
broad range of antimicrobial activity.
Methods:
In this study, we have used two pharmaceutically important drug molecules, namely dapsone and propofol, which are earlier reported as potent inhibitors of LPO. Whereas the stereochemistry
and mode of binding of dapsone and propofol to LPO is still not known because of the lack of the crystal structure of LPO
with these two drugs. In order to fill this gap, we utilized molecular docking and molecular dynamics (MD) simulation
studies of LPO in native and complex forms with dapsone and propofol.
Results:
From the docking results, the estimated
binding free energy (ΔG) of -9.25 kcal/mol (Ki = 0.16 μM) and -7.05 kcal/mol (Ki = 6.79 μM) was observed for dapsone,
and propofol, respectively. The standard error of Auto Dock program is 2.5 kcal/mol; therefore, molecular docking results
alone were inconclusive.
Conclusion:
To further validate the docking results, we performed MD simulation on unbound,
and two drugs bounded LPO structures. Interestingly, MD simulations results explained that the structural stability of
LPO-Propofol complex was higher than LPO-Dapsone complex. The results obtained from this study establish the mode
of binding and interaction pattern of the dapsone and propofol to LPO as inhibitors.
High overexpression of dye decolorizing peroxidase TfuDyP leads to the incorporation of heme precursor protoporphyrin IX
