PDBsum entry 1oy6

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Membrane protein PDB id
Protein chain
1006 a.a. *
* Residue conservation analysis

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Key reference
Title Structural basis of multiple drug-Binding capacity of the acrb multidrug efflux pump.
Authors E.W.Yu, G.Mcdermott, H.I.Zgurskaya, H.Nikaido, D.E.Koshland.
Ref. Science, 2003, 300, 976-980. [DOI no: 10.1126/science.1083137]
PubMed id 12738864
Multidrug efflux pumps cause serious problems in cancer chemotherapy and treatment of bacterial infections. Yet high-resolution structures of ligand transporter complexes have previously been unavailable. We obtained x-ray crystallographic structures of the trimeric AcrB pump from Escherichia coli with four structurally diverse ligands. The structures show that three molecules of ligands bind simultaneously to the extremely large central cavity of 5000 cubic angstroms, primarily by hydrophobic, aromatic stacking and van der Waals interactions. Each ligand uses a slightly different subset of AcrB residues for binding. The bound ligand molecules often interact with each other, stabilizing the binding.
Figure 1.
Fig. 1. Structures of the trimeric AcrB transporter with bound ligands viewed from the side parallel to the membrane. (A) AcrB with three bound R6G molecules. The figure shows the transmembrane domain (inner and outer leaflets), the periplasmic domain, and the location of cavity, vestibule, pore, and funnel (8). The drugs are bound approximately at the level of the outer surface of the membrane lipid bilayer. (B) through (D) show the center of the side view in (A), with bound Et, Dq, and Cip molecules. This figure and Fig. 2 were prepared with PyMOL (22).
Figure 2.
Fig. 2. The binding sites for the four ligands. Amino acid residues within 6 Å of the bound ligand molecules are shown. With the exception of (C), the view is approximately from the top (periplasmic side) of the trimer. Unmarked, primed, and double-primed residues, respectively, belong to the three subunits of the AcrB trimer. (A) R6G-binding site. (B) Et-binding site, including Phe^388 that is slightly farther away (see text). (C) Dq-binding site. The side view shows the binding of the two quinolinium moieties within each Dq molecule (as in Fig. 1). The phenylalanine residues interacting with the bottom quinolinium moieties are shown even though they are 6.3 Å away from the ligand. Ile^102 is not shown to avoid cluttering the figure. (D) Cip-binding site.
The above figures are reprinted by permission from the AAAs: Science (2003, 300, 976-980) copyright 2003.
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