Location of TMH1 and TMH7 residues selected for mutagenesis.

(A) Alignment of sequences of TMH1 and TMH7 of human P-gp with mutated residues shown in the box. (B) Location of TMH1 and TMH7 in a homology model of human P-gp derived from mouse P-gp (PDB.5KPI) in the inward-facing conformation (left) and the structure of the human P-gp E-Q mutant in the presence of ATP (PDB.6C0V) in the outward-facing conformation (right). TMH1 and TMH7 are colored green and cyan, respectively. The residues selected for mutation in TMH1,7 are shown as magenta (TMH1) and blue (TMH7) spheres. ECL1 and ECL4 are highlighted in red and orange, respectively. Cell membrane boundaries are marked. The figure was prepared in Pymol.