Crystallographic analysis of AcrB.

Purification, crystallization and preliminary diffraction studies of AcrB, an inner-membrane multi-drug efflux protein.

Resistance of pathogens to antibiotics is often dependent on multi-drug export proteins that reside in the inner membrane of bacteria. This work describes the expression, purification, crystallization and preliminary crystallographic analysis of AcrB of Escherichia coli. Together with AcrA and TolC, AcrB forms a proton motive force dependent efflux pump of the resistance-nodulation-cell divisio...

Structural basis of multiple drug-binding capacity of the AcrB multidrug efflux pump.

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 s...

X-ray crystallographic studies on bacterial proteins involved in active membrane transport: MalFGK2, MalE, ProX, and AcrB

Structural asymmetry of AcrB trimer suggests a peristaltic pump mechanism.

The AcrA/AcrB/TolC complex spans the inner and outer membranes of Escherichia coli and serves as its major drug-resistance pump. Driven by the proton motive force, it mediates the efflux of bile salts, detergents, organic solvents, and many structurally unrelated antibiotics. Here, we report a crystallographic structure of trimeric AcrB determined at 2.9 and 3.0 angstrom resolution in space gro...

Crystallographic Analysis of Drug and Inhibitor-Binding Structure of RND-Type Multidrug Exporter AcrB in Physiologically Relevant Asymmetric Crystals.

Xenobiotic extruding pumps have recently been known to be widely distributed in living organisms from mammalian to bacteria as a host-defense mechanism in cellular level. These pumps not only confer multidrug resistance of cancer cells and pathogenic bacteria but also cause hereditary diseases through the mutation. Our purposes are to elucidate the molecular structures and mechanisms of these x...