Fig. 1.
Partial state diagram for two drugs (A and B, each with two sites) acting on a receptor following the concerted transition scheme. Closed receptor states (R) occupy the plane at the bottom (note that some states are obscured such as B2RA) while open states (R*) occupy the plane at the top. The diagram is distorted to show states with only agonist A bound (solid line box at front), only agonist B bound (long dashed line box at left), and some states with both agonists bound (short dash box at right). In the absence of both A and B the receptor activates constitutively with L = R/R*. The value of the parameter L is a property of the receptor, not of any agonist. Agonist A binds to its site with dissociation constant KA on the closed receptor and KA* on the open receptor, with cA = KA*/KA. Note that the presence of bound B does not affect binding of A nor vice versa. The equilibrium between R and R* states is determined by the respective values for c, as dictated by detailed mass action in the coupled cycles (e.g., B2R/B2R* = cB2L and B2RA2/B2R*A2 = cB2cA2L).