Figure 6.

Schematized mechanism for conformational changes coupled to ATP hydrolysis in P-gp. A portion of the entire catalytic cycle is shown starting from the drug and nucleotide-bound state. After hydrolysis of one ATP, the conformational change and release of P_i are fast, preventing reformation of ATP or exchange of bound HPO₄^2– with H₂O. The conformational change is unlikely to include full dissociation of the NBD dimers but rather is fast with minor structural rearrangement. This conformational change is sufficient to ensure a high commitment to catalysis for ATP hydrolysis.