Extended Data Fig. 6. In silico modeling of the A2058 mutants.

(a) Water-mediated coordination of a macrolide antibiotic (ERY, green) by the wild-type A2058 nucleotide (blue) of the 23S rRNA. Existing H-bonds are shown by the black dashed lines. (b, c, d) Strong water-mediated coordination of a macrolide molecule on the ribosome becomes impossible when the adenine nucleotide at position 2058 of the 23S rRNA is mutated to guanine (b), cytosine (c), or uracil (d) nucleotides. Non-existing H-bonds (due to distance restraints) are shown by the grey dashed lines. Note that in the case of A2058G mutation, in addition to the inability of the guanine nucleotide to coordinate a macrolide via a water molecule, the exocyclic N2-amino group of guanine clashes with the C4-methyl group attached to the macrolactone ring of a macrolide molecule.