Related Experiment Video
Updated: Jun 6, 2026

In vitro Investigation of the MexAB Efflux Pump From Pseudomonas aeruginosa
Published on: February 17, 2014
Drug export and allosteric coupling in a multidrug transporter revealed by molecular simulations
Xin-Qiu Yao1, Hiroo Kenzaki, Satoshi Murakami
1Department of Biophysics, Graduate School of Science, Kyoto University, Kyoto 606-8502, Japan.
Abstract:
Multidrug resistance is a serious problem in current chemotherapy. The efflux system largely responsible for resistance in Escherichia coli contains the drug transporter, AcrB. The structures of AcrB were solved in 2002 as the symmetric homo-trimer, and then in 2006 as the asymmetric homo-trimer. The latter suggested a functionally rotating mechanism. Here, by molecular simulations of the AcrB porter domain, we uncovered allosteric coupling and the drug export mechanism in the AcrB trimer. Allosteric coupling stabilized the asymmetric structure with one drug molecule bound, which validated the modelling. Drug dissociation caused a conformational change and stabilized the symmetric structure, providing a unified view of the structures reported in 2002 and 2006. A dynamic study suggested that, among the three potential driving processes, only protonation of the drug-bound protomer can drive the functional rotation and simultaneously export the drug.
Related Concept Videos
The Significance of Membrane Transport
Transporters facilitate either an active or passive movement of solutes. They can allow a single-molecule transport down its...
Drug Absorption Mechanism: Carrier-Mediated Membrane Transport
Facilitated diffusion is a passive process that utilizes human Solute Carrier (SLC) transporters. These transporters bind to the drug, undergo structural...
ABC Transporters: Exporter
Cooperative Allosteric Transitions
Cooperative Allosteric Transitions
Cooperative Allosteric Transitions
