Figure 9.

Binding of midazolam to P450 3A4 (data from Ref. 32). P450 3A4 (2 μm) was mixed with midazolam (20 (red), 40 (green), 60 (dark blue), 80 (gold), 100 (light blue), and 150 (magenta) μm). A, double-exponential fits to data from (32) at varying midazolam concentrations. B, plots of biexponential rates (A) versus midazolam concentration: fast rate (■); slow rate (▴). C, fits to induced-fit model (Fig. 2) with k₁ = 3.6 × 10⁶ m⁻¹ s⁻¹, k₋₁ = 70 s⁻¹, k₂ = 3.4 s⁻¹, and k₋₂ = 4.5 s⁻¹ (ϵ_390–418 28 mm⁻¹ cm⁻¹). D, fits to conformation selection model (Fig. 2) with k₁ = 1.8 s⁻¹, k₋₁ = 1.6 s⁻¹, k₂ = 0.2 × 10⁶ m⁻¹ s⁻¹, and k₋₂ = 8.1 s⁻¹ (ϵ_390–418 10 mm⁻¹ cm⁻¹).