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
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 of AcrB residues. Several molecules ...