Supplementary Figure 6: Mutations that increase resistance to Api137.
From: An antimicrobial peptide that inhibits translation by trapping release factors on the ribosome
(a-c) Location of residues in (a) RF1 (orange) and (b, c) RF2 (teal) that increase resistance to Api137 when mutated. Site of mutations are shown in stick and surface representation and glutamines of the GGQ motif (Gln235 in RF1 and Gln252 in RF2) are shown as sticks for reference. (d-f) Location of Api137 resistance mutations in ribosomal proteins. (d) Lys63 in uL4 (blue) interacts with 23S rRNA residues G2061 and G2444. (e) Deletion of 82MKR84 (outside of the figure boundaries) in uL22 (purple) confers resistance to Api137 presumably by changing the geometry of the uL22 exit tunnel loop and disrupting Api137 interaction with neighboring 23S rRNA nucleotides (gray), such as A751. (f) The mutation of Arg81 in uL16 (brown) may relieve Api137-mediated RF1 and RF2 trapping by indirectly destabilizing interactions of deacylated tRNA with the P-site mediated by G2251 of the 23S rRNA.
