Bacterial 50S ribosomal subunit 23S rRNA peptidyl transferase center A-site (PTC A-site)

The Bacterial 50S ribosomal subunit 23S rRNA peptidyl transferase center (PTC) A-site is the primary functional locus within the large ribosomal subunit responsible for decoding and peptide bond formation (Polikanov et al., 2014, Molecular Cell, https://doi.org/10.1016/j.molcel.2014.09.020). It serves as the entry point for aminoacyl-tRNA molecules, which must correctly position their amino acid cargo for the peptidyl transferase reaction catalyzed by the 23S rRNA ribozyme (Wilson, 2014, Cold Spring Harbor Perspectives in Biology, https://doi.org/10.1101/cshperspect.a017954). This site is a critical target for several classes of antibiotics, including oxazolidinones, pleuromutilins, and phenicols, which disrupt bacterial growth by inhibiting protein synthesis (Eyal et al., 2015, Scientific Reports, https://doi.org/10.1038/srep16699). These drugs typically bind to the A-site or the A-site/P-site interface, sterically hindering the accommodation of tRNA or interfering with the catalytic environment (Long et al., 2006, Antimicrobial Agents and Chemotherapy, https://doi.org/10.1128/AAC.00658-06). Clinical challenges include the emergence of resistance through 23S rRNA mutations or enzymatic modification by Cfr methyltransferases, as well as potential host toxicity due to the structural homology between bacterial and human mitochondrial ribosomes (Leach et al., 2007, Molecular Pharmacology, https://doi.org/10.1124/mol.106.030015).

Other names

23S rRNA A-sitePeptidyl transferase center A-siteRibosomal A-siteAminoacyl-tRNA binding siteBacterial 50S A-site

Inhibition of bacterial protein synthesis by sterically blocking the binding of aminoacyl-tRNA to the A-site or by interfering with the catalytic environment required for the peptidyl transferase reaction.