Thioredoxin Glutathione Reductase from Schistosoma mansoni: An Essential Parasite Enzyme and a Key Drug Target
Figure 4
Time-Dependent Inactivation of S. mansoni TGR by OPZ
The time dependency of inactivation of S. mansoni TGR (15 pmol/μl) was revealed by determining the residual GR (A) and TrxR (C) activities of enzyme in the presence of 100 μM NADPH and inhibitor at 0, 2, 4, 10, and 30 min incubation periods. OPZ concentrations were 0 (•), 25 (□), 50 (♦), 75 (Δ), and 100 (▴) μM. All incubation mixtures included 2% final DMSO. The kobs data as a function of inhibitor concentration from the GR (B) or TrxR assay (D) versus OPZ concentrations followed a polynomial equation (not shown), suggesting that more than one binding site of OPZ is involved in the presence of different enzyme species of reacted and unreacted enzymes in mixture during the course of the inactivation process. The error bars in (B) and (D) represent ± the standard errors of the kobs values estimated separately at each inhibitor concentration, as obtained from nonlinear regression analysis.