3G5U
Structure of P-glycoprotein Reveals a Molecular Basis for Poly-Specific Drug Binding
Summary for 3G5U
| Entry DOI | 10.2210/pdb3g5u/pdb |
| Related | 3G60 3G61 |
| Descriptor | Multidrug resistance protein 1a, MERCURY (II) ION (2 entities in total) |
| Functional Keywords | p-glycoprotein, multidrug resistance, pgp, cyclic peptide, membrane protein |
| Biological source | Mus musculus (mouse) |
| Total number of polymer chains | 2 |
| Total formula weight | 286138.77 |
| Authors | Aller, S.G.,Yu, J.,Ward, A.,Weng, Y.,Chittaboina, S.,Zhuo, R.,Harrell, P.M.,Trinh, Y.T.,Zhang, Q.,Urbatsch, I.L.,Chang, G. (deposition date: 2009-02-05, release date: 2009-03-24, Last modification date: 2024-02-21) |
| Primary citation | Aller, S.G.,Yu, J.,Ward, A.,Weng, Y.,Chittaboina, S.,Zhuo, R.,Harrell, P.M.,Trinh, Y.T.,Zhang, Q.,Urbatsch, I.L.,Chang, G. Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. Science, 323:1718-1722, 2009 Cited by PubMed Abstract: P-glycoprotein (P-gp) detoxifies cells by exporting hundreds of chemically unrelated toxins but has been implicated in multidrug resistance (MDR) in the treatment of cancers. Substrate promiscuity is a hallmark of P-gp activity, thus a structural description of poly-specific drug-binding is important for the rational design of anticancer drugs and MDR inhibitors. The x-ray structure of apo P-gp at 3.8 angstroms reveals an internal cavity of approximately 6000 angstroms cubed with a 30 angstrom separation of the two nucleotide-binding domains. Two additional P-gp structures with cyclic peptide inhibitors demonstrate distinct drug-binding sites in the internal cavity capable of stereoselectivity that is based on hydrophobic and aromatic interactions. Apo and drug-bound P-gp structures have portals open to the cytoplasm and the inner leaflet of the lipid bilayer for drug entry. The inward-facing conformation represents an initial stage of the transport cycle that is competent for drug binding. PubMed: 19325113DOI: 10.1126/science.1168750 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.8 Å) |
Structure validation
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