Bacterial drug pumps

High-resolution structures of a multidrug efflux transporter responsible for bacterial resistance.

Andrea Rinaldi(

Bacterial resistance to multiple antibiotics and other drugs is a major, increasingly common problem throughout the world. Resistance is often associated with the overproduction of bacterial inner membrane proteins that are capable of extruding a variety of structurally unrelated drugs, antibiotics, and toxic compounds. In the May 9 Science, Edward Yu and colleagues at the University of California, Berkeley, disclose the structural basis of the activity of AcrAB, a constitutively expressed, major multidrug efflux system of Escherichia coli energized by proton motive force (Science, 300:976-980, May 9, 2003).

Yu et al. solved the high-resolution structures of AcrB crystallized in the presence of four structurally diverse ligands: rhodamine 6G, ethidium, dequalinium, and ciprofloxacin. Each substrate bound to different positions of the large central cavity — some 5000 cubic angstroms — of the transmembrane domain of the trimeric protein, each interacting mainly hydrophobically with a different subset...

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