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PDBsum entry 1oye
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Membrane protein
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PDB id
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1oye
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Structural basis of multiple drug-Binding capacity of the acrb multidrug efflux pump.
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Authors
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E.W.Yu,
G.Mcdermott,
H.I.Zgurskaya,
H.Nikaido,
D.E.Koshland.
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Ref.
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Science, 2003,
300,
976-980.
[DOI no: ]
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PubMed id
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Abstract
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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.
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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).
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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.
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The above figures are
reprinted
by permission from the AAAs:
Science
(2003,
300,
976-980)
copyright 2003.
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