Figure 4.

Structure of CAM-C4-TPP in complex with the 70S ribosome. (A) Overview of the drug-binding site (yellow) in the T. thermophilus 70S ribosome viewed as a cross-cut section through the nascent peptide exit tunnel. The 30S subunit is shown in light yellow, the 50S subunit is in light blue, ribosome-bound protein Y is colored green. (B) Superposition of the ribosome-bound CAM-C4-TPP (yellow) with the previous structures of CHL (green, PDB entry 6ND5 [2]) or CHL analog histidyl-CAM (blue, PDB entry 6CFJ [13]). All structures were aligned based on domain V of the 23S rRNA. (C,D) Close-up views of the CHL analog CAM-C4-TPP bound in the PTC and NPET of the 70S ribosome (E. coli numbering of the 23S rRNA nucleotides is used). Potential H-bond interactions are indicated with dashed lines. Note that by forming an H-bond with the base of nucleotide A2062 of the 23S rRNA (light blue) CAM-C4-TPP causes characteristic rotation of this nucleotide by approximately 160 degrees to form Hoogsteen base-pair with the m²A2503 of the 23S rRNA (red dashed arrow). N6 and N7 atoms of nucleotides A2062 and m²A2503 are highlighted in dark blue. The unrotated conformation of A2062 observed in the absence of the drug is shown in blue (PDB entry 4Y4P [32]).