Kinetics and Ligand-Binding Preferences of Mycobacterium tuberculosis Thymidylate Synthases, ThyA and ThyX
Figure 7
Inhibition of M. tuberculosis ThyA by 1843U89 and FdUMP.
(A) Titrations of mTHF (50, 150, 300, 600, 1200 µM) with varying concentrations of 1843U89 (•, 0 nM; ▾, 12.5 nM; ▪, 25 nM; ♦, 50 nM; ▴, 75 nM) in the presence of 3.75 µM dUMP. (B) Double reciprocal plot of data from plot A showing a noncompetitive inhibition mechanism. (C) Titrations of dUMP (1.25, 2.5, 5, 10 µM) with varying concentrations of FdUMP (•, 0 nM; ▾, 2.5 nM; ▪, 5 nM; ♦, 10 nM) in the presence of 142.9 µM mTHF. (D) Double reciprocal plot of data from plot C showing a noncompetitive inhibition mechanism. Lines in A and C are plots of Michaelis-Menten equations with calculated constants. Lines in B and D are linear regressions. Error bars are propagation of standard deviations.