50S ribosomal subunit peptidyl transferase center (PTC) (PTC)

The 50S ribosomal subunit peptidyl transferase center (PTC) is the catalytic core of the bacterial ribosome, situated within the 23S ribosomal RNA (rRNA). It functions as a ribozyme, facilitating the formation of peptide bonds between the aminoacyl-tRNA in the A-site and the peptidyl-tRNA in the P-site during translation (Polacek & Mankin, 2005, "The ribosomal peptidyl transferase center: structure and function"). This site is a major pharmacological target for diverse classes of antibiotics, including macrolides, oxazolidinones, lincosamides, and pleuromutilins (Wilson, 2014, "Ribosome-targeting antibiotics and mechanisms of bacterial resistance"). These agents interfere with protein synthesis by either physically blocking the formation of the peptide bond or obstructing the nascent peptide exit tunnel (Dunkle et al., 2010, "Structures of the bacterial ribosome in intermediate states of translocation"). Because the PTC is highly conserved, it is a focus of intense research for treating multi-drug resistant bacterial infections. However, its structural similarity to the human mitochondrial ribosome can lead to clinical toxicities, such as bone marrow suppression, when certain inhibitors are used for prolonged periods (StatPearls, 2023, "Linezolid"). Resistance to PTC-targeting drugs often arises through mutations in the 23S rRNA or enzymatic modifications like methylation (Long et al., 2006, "The Cfr rRNA methyltransferase confers resistance to Phenicols, Lincosamides, Oxazolidinones, Pleuromutilins, and Streptogramin A antibiotics").

Other names

Peptidyl transferase center23S rRNA peptidyl transferase centerRibosomal PTCLarge ribosomal subunit peptidyl transferase center

Inhibition of bacterial protein synthesis by binding to the 23S rRNA within the 50S subunit, thereby blocking peptide bond formation or sterically hindering the passage of the nascent peptide chain through the exit tunnel.