LeuT substrate and inhibitor binding sites. x-ray crystal structures of LeuT in complex with leucine (PDB accession no. 2A65; A), leucine and OG (3GJC; B), and leucine and clomipramine, a TCA (2Q6H; C). The ligands in the structures are represented as spheres and the residues forming the S2 site are shown in blue. Residues Y108 and F253, which are occluding leucine bound to S1 from the extracellular solution, are shown in orange. The broken lines pass through S1 and S2 to indicate the position in the binding sites.