(A) Characteristic structural features used to define the outward-facing open (or outward-open for simplicity) and inward-facing open (or inward-open) states of hDAT. The equivalent residues for Phe76, Ser422, and S429 of hDAT in dDAT, LeuT, and hSERT are shown in the insect. The distances between Cα atoms of Phe76 and Ser422 and between Phe76 and Ser429 are used to denote the corresponding distances in different transporters. (B) The relative positions of Phe76, Ser422, and Ser429 in the outward-open (blue) and inward-open (red) states of hDAT(1–604). (C) The relative positions of Phe76, Ser422, and Ser429 in the outward-facing (blue) and inward-facing (red) states of AMPH-bound p-hDAT(1–604). OF, IF, OFo, and, IFo denote outward-facing open, inward-facing open, outward-facing occluded, and inward-facing occluded, respectively.