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Figure 4.
Fig. 4. Model of substrate transport by P-gp. (A) Substrate
(magenta) partitions into the bilayer from outside of the cell
to the inner leaflet and enters the internal drug-binding pocket
through an open portal. The residues in the drug-binding pocket
(cyan spheres) interact with QZ59 compounds and verapamil in the
inward-facing conformation. (B) ATP (yellow) binds to the NBDs
causing a large conformational change presenting the substrate
and drug-binding site(s) to the outer leaflet and/or
extracellular space. In this model of P-gp, which is based on
the outward-facing conformation of MsbA and Sav1866 (13, 14),
exit of the substrate to the inner leaflet is sterically
occluded, which provides unidirectional transport to the outside.
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