Compromised conformation and kinetics of catalase in the presence of propylthiouracil: A biophysical study and alleviation by curcumin

In the present study, the inhibitory effect of propylthiouracil (PTU) on bovine liver catalase (BLC) activity was studied in the presence of curcumin (CUR). The results suggest that the PTU-induced decrease in BLC activity was caused by a change in conformation of BLC with reduced alpha-helical content and decrease in zeta potential. Nevertheless, temperature-dependent activation of CUR protects the activity of BLC by restoring the secondary conformation and zeta potential of BLC. CUR inhibited the time-induced reduction in BLC activity and the protection was increased with increasing concentrations of CUR and found to be significant even from 1:0.1 molar ratios. The enzyme kinetics confirmed the high catalytic efficiency of BLC in presence of CUR than PTU. The protective role of CUR was due to the formation of a more stabilized complex as demonstrated by molecular docking, and fourier-transform infrared study. Isothermal titration calorimetric study supports for a favourable reaction between BLC and PTU or CUR due to the negative Delta H, and positive T Delta S. Although the number of binding sites for PTU and CUR was found to be 10 and 7, respectively, the binding affinity between CUR and BLC is approximately 3.72 fold stronger than BLC-PTU complex. The increased melting temperature of BLC was noticed in presence of CUR suggesting the protective potential of CUR towards biomolecules. Indeed, this is the first biophysical study to describe the molecular mechanism of PTU-induced reduction in BLC activity and alleviation by CUR with detail kinetics. Thus, CUR can be further extended to other antioxidant enzymes or compromised biomolecules for therapeutic interventions.

Automated summary

This study explored the inhibitory effect of PTU on BLC activity and the protective role of CUR. The results showed that PTU reduced BLC activity by changing its conformation and zeta potential, while CUR restored the secondary conformation and protected BLC activity. CUR inhibited the time-induced reduction in BLC activity and its protection was concentration-dependent. The binding affinity between CUR and BLC was stronger than BLC-PTU complex. This study provides detailed insights into the molecular mechanism of PTU-induced reduction in BLC activity and its alleviation by CUR, suggesting the potential therapeutic applications of CUR.