Mycobacterial 70S ribosome (70S ribosome)

The mycobacterial 70S ribosome is the essential macromolecular machine responsible for protein synthesis in Mycobacterium species, most notably Mycobacterium tuberculosis (Li et al., 2017, Nature Communications). It consists of two major subunits, the 30S and 50S, which work in tandem to decode mRNA and catalyze the formation of polypeptide chains. This ribosome is a validated therapeutic target because its inhibition leads to bacterial cell death or growth arrest, and it possesses unique structural features—such as specific ribosomal protein extensions and unique rRNA modifications—that distinguish it from other bacterial ribosomes and the eukaryotic 80S ribosome (Wilson, 2014, Nature Reviews Microbiology). Clinically significant antibiotics, including aminoglycosides like streptomycin and oxazolidinones like linezolid, exert their effects by binding to specific sites on the ribosomal subunits to disrupt translation initiation or elongation (WHO, 2023). Resistance to these drugs often arises from mutations in the ribosomal RNA (rRNA) or ribosomal proteins, making the study of this target vital for addressing multi-drug resistant tuberculosis. Recent cryo-electron microscopy studies have highlighted mycobacteria-specific features that are being leveraged to develop more selective and potent anti-tubercular agents.

Other names

Mycobacterium tuberculosis ribosomeM. tuberculosis 70S ribosomeBacterial 70S ribosome (Mycobacterial)Mycobacterial translation machinery

Drugs targeting the mycobacterial 70S ribosome inhibit protein synthesis by binding to specific sites on either the 30S or 50S subunits. Aminoglycosides bind the 30S subunit to induce mRNA misreading and inhibit translocation (Wilson, 2014, Nature Reviews Microbiology). Oxazolidinones bind the 50S subunit at the peptidyl transferase center (PTC) to prevent the formation of the 70S initiation complex (DrugBank Online, 2024). Macrolides block the nascent peptide exit tunnel on the 50S subunit, leading to premature dissociation of peptidyl-tRNA.