Extended Data Fig. 4: Analysis of the orientation of the dimethyl-amino group in previously published structures of ribosome-bound macrolides.

a, b, In the structures of erythromycin (ERY) in complex with H. marismortui 50S subunit (blue, PDB entry 1YI2²²), or T. thermophilus 70S ribosome (green, PDB entry 4V7X²³) the nitrogen lone pair of electrons on the dimethyl-amino group of the desosamine sugar is oriented towards the exocyclic N6-amino group of the A2059 nucleotide of the 23S rRNA (blue), as indicated by the yellow arrow. Note that the formation of a direct H-bond, in this case, is impossible due to the large distance between the potential interacting partners (grey dashed lines). H-bond between 2’-OH group of desosamine sugar and N1 atom of A2058 is shown by the black dashed lines. c, d, In the structures of azithromycin (AZI) in complex with H. marismortui 50S subunit (orange, PDB entry 1YHQ²²), or T. thermophilus 70S ribosome (orange, PDB entry 4V7Y²³) the nitrogen lone pair of electrons of the dimethyl-amino group on the desosamine is rotated by approximately 90 degrees away from the residue A2059 in the direction of residue A2058, as indicated by the yellow arrow. Note that, in this case, there are no obvious binding partners for this group on the ribosome.