Broad-specificity efflux pumps and their role in multidrug resistance of Gram-negative bacteria - PubMed (original) (raw)
A. The “deep” binding site for minocycline and doxorubicin found by Murakami and coworkers (Murakami et al., 2006). The orientation of the trimeric protein is shown in the inset, in which each protomer is shown in different color (Access, mauve; Binding, sand; and Extrusion, green). The binding pocket is shown as an orange-colored surface, with the bound minocycline molecule in stick representation. The site consists of two subpockets, the narrow “Groove” and the much wider “Cave.” The amino acid residues shown in the surface representation were specified earlier (Takatsuka et al., 2010). Parts of the protein close to the viewer have been clipped away to show the site more clearly. B. The two plausible binding sites of AcrB. This shows the “deep”, “ultimate” binding site shown in A (as orange surface), as well as the putative site on the surface of the periplasmic domain, at the entrance of the large cleft (as green surface). The residues used to generate the latter surface are residues 566, 664, 666, 668, 673, 676, 717, and 828, identified by Husain and Nikaido (2010). To get this view, the model was rotated by 70° as shown at the bottom. No clipping was applied here. C. A possible path for the substrate, from the surface site (green surface) to the deep site (orange surface), with the tunnel shown in gray. This is a view from the top, and the presumed direction of the substrate flow is shown by an arrowhead. The tunnel was detected by the program Caver (
), and all figures were generated by using Pymol (
).