Figure 6. Proposed mechanism of increased eNOS NO release by Cavnoxin and F92A–Cav-1.

eNOS (oval) is thought to exist in a dynamic balance between a “more active” state (free of Cav-1 inhibitory clamp, left side) and a “less active” state (bound to and inhibited by endogenous Cav-1, lower panel). Our data show that F92A–Cav-1 and Cavnoxin can bind eNOS (left) and prevent its inhibition by endogenous Cav-1, resulting in the creation of a third dynamic state characterized by an eNOS bound to a noninhibitory Cav-1 scaffolding domain containing the F92A substitution (lower panel, far right), thereby shifting eNOS equilibrium toward a “more active” state by preventing the inhibitory clamp of endogenous Cav-1.