Mycobacterium tuberculosis 50S ribosomal subunit peptidyl transferase center (Mtb 50S PTC)

The Mycobacterium tuberculosis 50S ribosomal subunit peptidyl transferase center (PTC) is a highly conserved catalytic site located within the 23S ribosomal RNA (rRNA) of the large ribosomal subunit. Its primary biological function is to facilitate peptide bond formation by orienting the aminoacyl-tRNA and peptidyl-tRNA molecules during protein translation (PMID: 11054804). In Mycobacterium tuberculosis, the PTC is a validated therapeutic target for oxazolidinone antibiotics, such as linezolid and tedizolid, which are essential for treating multidrug-resistant tuberculosis (MDR-TB) (PMID: 24920651). These drugs bind to the PTC and sterically inhibit the formation of the 70S initiation complex or the translocation process, effectively halting bacterial growth. However, prolonged use of drugs targeting the PTC can lead to host toxicity, such as myelosuppression and neuropathy, due to the structural similarity between bacterial ribosomes and human mitochondrial ribosomes (PMID: 12654743). Resistance to these agents typically arises through specific mutations in the 23S rRNA or ribosomal proteins like L3 (rplC), which alter the drug-binding pocket (PMID: 28807910). The PTC remains a focus of drug development to create next-generation oxazolidinones with improved safety profiles and activity against resistant strains.

Other names

23S rRNA peptidyl transferase centerPTCLarge ribosomal subunit peptidyl transferase centerMtb 50S ribosomal subunit

Inhibition of bacterial protein synthesis by binding to the peptidyl transferase center (PTC) of the 50S ribosomal subunit, preventing the formation of the peptide bond or the initiation complex.