Figure 1.

Inhibition of Mtb proteasome by fellutamide B (1)

A) Structure of 1. B) Reaction progress curves of cleavage of Suc-LLVY-AMC by Mtb proteasome in the absence and presence of 1 at 6.25 nM – 40 nM; the curves were fit by nonlinear regression to equation (1) to determine the apparent first-order rate constant k_obs values, which were corrected by equation (2) to yield real k_obs. C) Dependence of k_obs on inhibitor concentration. The solid line was drawn by fitting the data to equation (3), yielding k_on = (129 ± 0.8) × 10³ M⁻¹s⁻¹, and k_off = (0.96 ± 0.13) × 10⁻³ s⁻¹. D) Plot of v_s/v_o versus inhibitor concentration. The data were fitted to equation (4), yielding K_i = 6.8 ± 0.2 nM.