Bacterial 50S ribosomal subunit peptidyl transferase center (PTC)

The bacterial 50S ribosomal subunit peptidyl transferase center (PTC) is the catalytic core of the ribosome, responsible for synthesizing proteins by facilitating peptide bond formation (Steitz & Moore, 2003). Located within the 23S ribosomal RNA, the PTC acts as a ribozyme that correctly orients the aminoacyl-tRNA and peptidyl-tRNA substrates to allow for the nucleophilic attack necessary for polypeptide elongation. Because protein synthesis is vital for bacterial growth, the PTC is a major target for several classes of antibiotics, including oxazolidinones, lincosamides, and pleuromutilins (Polikanov et al., 2014). These drugs bind to the PTC to physically obstruct the binding of tRNA or the movement of the growing peptide chain through the exit tunnel. However, the structural similarity between bacterial and human mitochondrial ribosomes can lead to clinical safety concerns, such as myelosuppression, due to off-target inhibition of mitochondrial translation (Leach et al., 2007). Additionally, the clinical utility of PTC-targeting drugs is frequently challenged by the emergence of resistance mechanisms, such as rRNA mutations or the acquisition of the cfr methyltransferase gene (Long et al., 2006).

Other names

Peptidyl transferase center50S PTCRibosomal peptidyl transferase center23S rRNA peptidyl transferase centerLarge ribosomal subunit peptidyl transferase center

Inhibition of bacterial protein synthesis by binding to the peptidyl transferase center (PTC) of the 50S ribosomal subunit, which prevents the formation of peptide bonds or sterically blocks the nascent peptide exit tunnel (Wilson, 2014).