Mycobacterial 50S ribosomal subunit peptidyl transferase center (PTC)

The Mycobacterial 50S ribosomal subunit peptidyl transferase center (PTC) is the highly conserved catalytic site within the large ribosomal subunit where peptide bond formation occurs during translation (Wilson, 2014). It is primarily composed of 23S ribosomal RNA (rRNA), making it a ribozyme that facilitates the nucleophilic attack of the aminoacyl-tRNA on the peptidyl-tRNA (Richter et al., 2007). In mycobacteria, particularly Mycobacterium tuberculosis, the PTC is a major therapeutic target for several antibiotic classes, including oxazolidinones (e.g., linezolid) and macrolides (e.g., clarithromycin), which bind to the site and disrupt protein synthesis (Belousoff et al., 2017). Because the PTC is essential for bacterial viability, its inhibition is an effective strategy for treating tuberculosis and other mycobacterial infections. However, the structural similarity between the bacterial PTC and the human mitochondrial ribosome can lead to clinical toxicities such as myelosuppression and neuropathy (Long & Vester, 2012). Resistance to PTC-targeting drugs often emerges through point mutations in the 23S rRNA or modifications by methyltransferases, necessitating the development of next-generation inhibitors.

Other names

23S rRNA peptidyl transferase centerRibosomal peptidyl transferase center50S PTCPeptidyl transferase site

Drugs targeting the PTC typically bind to the A-site or P-site of the 23S rRNA, sterically hindering the binding of aminoacyl-tRNA or the formation of the peptide bond, thereby inhibiting bacterial protein synthesis (Wilson, 2014; Belousoff et al., 2017).