Figure 5.

Ligand binding to the drug binding pocket of P-glycoprotein: RRR stereoisomer of the cyclic inhibitor QZ59 binding. The left side of each panel shows the results of docking to three sequential TMD frames bracketing the fully opened inward conformation of the human Pgp model. The right side of each frame shows the crystal structure of mouse Pgp with QZ59_RRR bound. (A) First frame of the cyclic peptide docking to human Pgp as licorice with the positions of side chains in the subsequent two frames (see panels B and C) shown with thin lines. (B and C) Two subsequent frames as licorice with previous and/or subsequent frames shown with thin black lines. Panel D shows the respective positions of the homologous residues that make up the binding pocket for QZ59-RRR as identified by ref (17): left side, human Pgp model; right side, mouse Pgp crystal structure.