Fig. 4

Model of P-glycoprotein action. Under physiological conditions (high ATP, no allocrite) the inward-facing state (a) predominates over the outward-facing state (b) which is unstable because of bringing together negative charges (red dashes, red circle). Allocrite binding (green hexagon) increases the chances of formation of the outward facing state and export of the allocrite to the outside. Hydrolysis of ATP can occur during the lifetime of the outward-facing state and hence there is a finite chance of forming the post-hydrolytic state (c), even in the absence of allocrite. Dissociation of inorganic phosphate (Pi) and ADP results in the formation of the transient apo-state (inward-facing, d) before ATP re-binds and returns the system to the starting point (a). The thickness of the two-way arrows at stages 1–4 indicate the relative proportions of the different paired states, but are not intended to be quantitative