Model of FMN domain function in electron transfer and heme reduction. Two hinge elements (H1 and H2) connect the FMN domain in NOS enzymes. The interactions required for electron transfer can be described by a two-equilibrium, three-state model. In equilibrium A, nNOS fluctuates between a closed conformation competent for FMN-FAD/NADPH electron transfer (FMN-shielded, left) and an open conformation where the FMN domain can interact with electron acceptors such as cytochrome c (FMN-deshielded, center). In equilibrium B, nNOS fluctuates between the FMN-deshielded conformation and a conformation competent for FMN to heme electron transfer. Complementary surface charge interactions (gray, negative, and black, positive) are involved in the domain interactions. See text for details.