Figure 5.

Intramolecular water-accessible channels in the AcrB trimer (Nakashima et al., 2011). The channels are shown as colored solid surfaces, as calculated using the CAVER program (Medek et al., 2007). The proximal pocket, distal pocket, entrances and funnel-like exit are depicted in green, pink, gray, and yellow, respectively. The channel apertures at the entrance and exit are depicted in black. (1) Inner membrane entrance (Murakami et al., 2006), (2) periplasmic entrance (Seeger et al., 2006), (3) central cavity entrance (Nakashima et al., 2011). (A) Side view. The channels in the access monomer behind the figure have been omitted. The central cavity and central hole are depicted as dotted lines. (B) Horizontal cut view of the porter domain. The yellow circle indicates the closed pore-like structure comprising three central α-helices (depicted as a ribbon model with dense color), which was postulated to be a part of the putative substrate translocation channel during the early stages, however, it was not the case. The central α-helix of extrusion monomer is inclined 15° toward binding monomer more than the other two α-helices and, as a result, blocks the exit from the drug binding site. Bound minocycline (cyan), doxorubicin (orange), rifampicin (magenta), and erythromycin (yellow) overlap in the space-filling model.