Figure 5 |. A water molecule mediates the interaction of macrolides with the ribosome.

(a, b) High-resolution 2F_o-F_c electron density maps (blue mesh) of ribosome-bound ERY (green, A) and TEL (magenta, B) show that the dimethyl-amino group of a macrolide is rotated towards A2058 and forms an H-bond with a water molecule (yellow) that is tightly coordinated by the exocyclic N6-amino group of A2058 and the phosphate of G2505. The view in the middle insets is from the top along the H-bond, connecting the G2505 phosphate with the water. (c) Detailed arrangement of the H-bonds formed by the desosamine sugar of a macrolide (green) with 23S rRNA (blue) of the ribosome via a water molecule (yellow). Hydrogens are colored white; nitrogens blue; oxygens red (except for the water). H-bonds are shown with dashed lines. (d) Superpositioning of the new structures of ribosome-bound ERY with the new structure of the A2058-dimethylated 70S ribosome showing the clash between one of the m₂⁶A2058 methyl groups and the water molecule. (e) Schematic diagram showing the molecular mechanism of resistance of A2058-dimethylated ribosomes to macrolide antibiotics. Note that due to the inability of the dimethyl-amino group of the m⁶₂A2068 residue to serve as an H-bond donor, it cannot participate in the coordination of the water molecule on the ribosome. Moreover, the methyl groups physically displace the water molecule leaving the G2505 phosphate and the dimethyl-amino group of macrolide desosamine without an H-bond partner.