title: Role of water during the extrusion of substrates by the efflux transporter AcrB.
abstract: The major efflux system in Escherichia coli is the tripartite complex AcrAB-TolC. Its homotrimeric transporter AcrB is polyspecific and extrudes antibiotics out of the bacterium. This extrusion is performed via a functional rotation, in which each monomer assumes a particular conformation. In the present study, targeted molecular dynamics simulations have been employed to obtain a molecular level understanding of the transport process. A particular focus is put on the role of water molecules in this extrusion process. It is shown that the water flows from the binding pocket toward the exit gate in the extrusion step and helps the substrate to move along this path. These results are underpinned by a detailed analysis of the electrostatic interaction energy. Furthermore, the role of water for the polyspecificity of the transporter is discussed.
authors.affiliation: School of Engineering and Science, Jacobs University Bremen, Bremen, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Schulz
authors.forename: Attilio V
authors.initials: AV
authors.lastname: Vargiu
authors.forename: Paolo
authors.initials: P
authors.lastname: Ruggerone
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kleinekathöfer
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000737:chemistry*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014867:Water / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D014867:Water; C083496:AcrB protein, E coli