Extended Data Fig. 7: High-resolution electron density maps of iboxamycin (IBX) bound to the bacterial ribosome. | Nature

Extended Data Fig. 7: High-resolution electron density maps of iboxamycin (IBX) bound to the bacterial ribosome.

From: A synthetic antibiotic class overcoming bacterial multidrug resistance

Extended Data Fig. 7

a, b, Unbiased Fo-Fc and 2Fo-Fc electron density maps of IBX in complex with the T. thermophilus 70S ribosome (green and blue mesh, respectively). The refined model of IBX is displayed in its electron density before (a) and after (b) the refinement contoured at 3.0σ and 1.5σ, respectively c, Superposition of ribosome-bound IBX (yellow) with prior structures of clindamycin bound to the tRNA-free 70S ribosome from eubacterium E. coli (blue, PDB entry 4V7V30) or to the 50S ribosomal subunit from archaeon H. marismortui harboring the 23S rRNA mutation G2099A (green, PDB entry 1YJN48). All structures were aligned based on domain V of the 23S rRNA. d, 2Fo-Fc electron density map (blue mesh) corresponding to ribosome-bound IBX (yellow), deacylated A-site tRNAPhe (green) and aminoacylated initiator P-site fMet-NH-tRNAiMet (dark blue). The refined models of tRNAs are displayed in their respective electron-density maps contoured at 1.0σ. In d, the entire bodies of the A- and P-site tRNAs are viewed from the back of the 50S subunit, as indicated by the inset. Ribosome subunits are omitted for clarity. Note that IBX binding to the ribosome prevents accommodation of the aminoacyl-bearing CCA-end of the A-site tRNA. e, Close-up view of the P-site tRNA CCA-end bearing a formyl-methionyl (cyan) residue. f, Detailed arrangement of the hydrogen bonds formed between the aminooctose component of IBX with 23S rRNA residues A2058 and G2505 (light blue).

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