substrate enters p-gp either from an opening within the inner leaflet of the membrane or from an opening at the cytoplasmic side of the protein. atp binds at the cytoplasmic side of the protein. following binding of each, atp hydrolysis shifts the substrate into a position to be excreted from the cell. release of the phosphate (from the original atp molecule) occurs concurrently with substrate excretion. adp is released, and a new molecule of atp binds to the secondary atp-binding site. hydrolysis and release of adp and a phosphate molecule resets the protein, so that the process can start again.