Fig. 2.
Structure, and dynamical and steady-state behaviors of Model 3a. (A) Structure of Model 3a featuring two-step ETGE binding and interaction with class I–V activator. (B) Dynamical changes of basal NRF2free, KEAP1_NRF2open1, KEAP1_NRF2open2, KEAP1_NRF2closed, and NRF2tot in response to termination of NRF2 synthesis (by setting k0 = 0) starting at 0 min with k6 at default value. (C) Dynamical changes of various NRF2 species in response to stabilization of NRF2 in KEAP1_NRF2closed by setting k6 = 1.252E-4 starting at 0 min and in response to termination of NRF2 synthesis (by setting k0 = 0) starting at 500 min. For simulations in (B) and (C), CLASSI-V level is kept at zero. Dynamical changes of (D)NRF2tot, (E)NRF2free, and (F)KEAP1free_tot in response different levels of CLASSI-V with k’6 at default value. (G) Steady-state dose-response curves of various NRF2 species and KEAP1free_tot on double-log scale with k’6 at default value. Shown are nH and LRCmax for NRF2free; nH and LRCmax for NRF2total are 1.22 and 0.42 respectively (not shown). (H–I) Flux analyses for conditions when NRF2 in KEAP1_NRF2closed is stabilized by setting k6 to 30% (H) and 10% (I) of default value.