Extended Data Fig. 9: Effect of TcmX on the accommodation of the 3’ end of aminoacyl-tRNA, on 23S rRNA residue 2602 and on the N-terminus of ribosomal protein bL27.
From: Tetracenomycin X sequesters peptidyl-tRNA during translation of QK motifs
a–d, Structural comparison of 23S rRNA nucleotides and tRNAs within the A site (a, b) and P site (c, d) regions of the peptidyl transferase center in the uninduced (Ref. 21) and induced (pre-attack) (Ref. 22) states (PDB 1VQ6 and 1VY4, respectively) (a, c), and the uninduced and TcmX-inhibited states (b, d). In the 70S–MAAAPQKC–TcmX structure, 23S rRNA residues U2506, G2583 and U2584 are in their induced conformation, but 23S rRNA nucleotide U2585 and nucleotide A76 of the P-site tRNA remain in the uninduced conformation, indicating partial aminoacyl-tRNA accommodation into the peptidyl transferase center. e, Sequestration of residue A76 of the P-site tRNALys within the tunnel by TcmX causes the preceding residue C75 to shift, which in turn leads to a conformational change in the peptidyl transferase center resulting in the stacking of the base of 23S rRNA residue A2602 against the imidazole ring of residue His-3 of ribosomal protein bL27.
