4Q9K: P-glycoprotein Cocrystallised With Qz-leu

P-glycoprotein (P-gp) is a transporter of great clinical and pharmacological significance. Several structural studies of P-gp and its homologs have provided insights into its transport cycle, but questions remain regarding how P-gp recognizes diverse substrates and how substrate binding is coupled to ATP hydrolysis. Here, four new P-gp co-crystal structures with a series of rationally designed ligands are presented. It is observed that the binding of certain ligands, including an ATP-hydrolysis stimulator, produces a large conformational change in the fourth transmembrane helix, which is positioned to potentially transmit a signal to the nucleotide-binding domains. A new ligand-binding site on the surface of P-gp facing the inner leaflet of the membrane is also described, providing vital insights regarding the entry mechanism of hydrophobic drugs and lipids into P-gp. These results represent significant advances in the understanding of how P-gp and related transporters bind and export a plethora of metabolites, antibiotics and clinically approved and pipeline drugs.
PDB ID: 4Q9KDownload
MMDB ID: 127454
PDB Deposition Date: 2014/5/1
Updated in MMDB: 2016/05
Experimental Method:
x-ray diffraction
Resolution: 3.8  Å
Source Organism:
Mus musculus
Similar Structures:
Biological Unit for 4Q9K: dimeric; determined by author
Molecular Components in 4Q9K
Label Count Molecule
Proteins (2 molecules)
Multidrug Resistance Protein 1A(Gene symbol: Abcb1a)
Molecule annotation
(30f)l(30f)l(30f)l Peptide
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB