Kinetic behavior of the major multidrug efflux pump AcrB of Escherichia coli

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Kinetic behavior of the major multidrug efflux pump AcrB of Escherichia coli.

Multidrug efflux transporters, especially those that belong to the resistance-nodulation-division (RND) family, often show very broad substrate specificity and play a major role both in the intrinsic antibiotic resistance and, with increased levels of expression, in the elevated resistance of Gram-negative bacteria. However, it has not been possible to determine the kinetic behavior of these im...

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Mechanism of recognition of compounds of diverse structures by the multidrug efflux pump AcrB of Escherichia coli.

The AcrB trimeric multidrug efflux transporter of Escherichia coli pumps out a very wide spectrum of compounds. Although minocycline and doxorubicin have been cocrystallized within the large binding pocket in the periplasmic domain of the binding protomer, nothing is known about the binding of many other ligands to this protein. We used computer docking to evaluate the interaction of about 30 c...

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Substrate-dependent dynamics of the multidrug efflux transporter AcrB of Escherichia coli.

The resistance-nodulation-cell division (RND)-type xenobiotic efflux system plays a major role in the multidrug resistance of gram-negative bacteria. The only constitutively expressed RND system of Escherichia coli consists of the inner membrane transporter AcrB, the membrane fusion protein AcrA, and the outer membrane channel TolC. The latter two components are shared with another RND-type tra...

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Site-directed mutagenesis reveals putative substrate binding residues in the Escherichia coli RND efflux pump AcrB.

The Escherichia coli multidrug efflux pump protein AcrB has recently been cocrystallized with various substrates, suggesting that there is a phenylalanine-rich binding site around F178 and F615. We found that F610A was the point mutation that had the most significant impact on substrate MICs, while other targeted mutations, including conversion of phenylalanines 136, 178, 615, 617, and 628 to a...

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AcrA, AcrB, and TolC of Escherichia coli Form a Stable Intermembrane Multidrug Efflux Complex.

Many transporters of Gram-negative bacteria involved in the extracellular secretion of proteins and the efflux of toxic molecules operate by forming intermembrane complexes. These complexes are proposed to span both inner and outer membranes and create a bridge across the periplasm. In this study, we analyzed interactions between the inner and outer membrane components of the tri-partite multid...

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ژورنال

عنوان ژورنال: Proceedings of the National Academy of Sciences

سال: 2009

ISSN: 0027-8424,1091-6490

DOI: 10.1073/pnas.0901695106