Fig. 1: Substrate positioning in the PTC.
a, Schematic depicting peptide bond formation in the ribosome active site known as the PTC. The PTC promotes peptide bond formation by positioning the nucleophilic α-amino group (Nα) of one substrate, the A-site aminoacyl-tRNA, near the electrophilic sp2-hybridized carbonyl carbon (Csp2) of the second substrate, the P-site peptidyl-tRNA. Attack by Nα generates a tetrahedral intermediate that subsequently breaks down to product: a peptidyl-tRNA carrying an additional C-terminal amino acid. Cytidine residues of the tRNAs’ 3′-CCA ends are represented by the letter ‘C’ in a yellow circle. b, Cryo-EM density (indigo surface) and our model for Met residues in the PTC. The distance between the A-site (green) nucleophilic amine and the P-site (rose) carbonyl carbon (3.3 Å) is indicated with a black dotted line. The 23S rRNA is shown in white. The Mg2+ ion that coordinates the C75–A76 internucleotide phosphate is shown in green. Note that an amide linkage is shown between the A76 and Met residues of each tRNA to reflect the experimental substrates used for structure determination; however, for simulation, this was replaced with the ester linkage that would be present during an elongation reaction. The map here was post-processed with a B-factor of –13 Å2 and supersampled for smoothness. c, Alternative view of the A-site and P-site Met residues highlighting the planes of the carbonyl that define the Bürgi–Dunitz (αBD) and Flippin–Lodge (αFL) angles and the geometry of nucleophilic attack.
