Target intelligence / Profile preview

Bacterial 50S ribosomal subunit (50S) (50S)

Target
50S
Molecular classification
Ribonucleoprotein complex, Ribosome, Translation machinery
01

Overview

The bacterial 50S ribosomal subunit is the larger component of the prokaryotic 70S ribosome, playing a critical role in protein biosynthesis (Wilson, D. N., 2014, Nature Reviews Microbiology). It contains the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds between amino acids, and the exit tunnel through which the growing polypeptide chain leaves the ribosome (Polikanov et al., 2012, Molecular Cell). Because of its essential role in bacterial survival and its structural differences from the eukaryotic 60S subunit, it is a primary target for several classes of antibiotics, including macrolides, lincosamides, and oxazolidinones (Dunkle et al., 2010, Science). These drugs typically bind to the 23S rRNA within the subunit to disrupt translation, effectively halting bacterial growth or causing cell death (StatPearls, 2023). However, the similarity between bacterial ribosomes and human mitochondrial ribosomes can lead to off-target effects and toxicity during prolonged treatment (Erakovic et al., 2020, Antibiotics). Understanding the structural nuances of the 50S subunit is vital for overcoming emerging antibiotic resistance mechanisms, such as ribosomal methylation or mutations in the binding sites (Vester & Douthwaite, 2001, Antimicrobial Agents and Chemotherapy).

Other names
Large ribosomal subunit50S subunitBacterial 50S ribosomeProkaryotic 50S subunit
02

Mechanism of action

Inhibition of bacterial protein synthesis by binding to the 23S rRNA of the 50S subunit, which interferes with peptidyl transferase activity, inhibits the translocation of the peptidyl-tRNA, or physically blocks the exit of the nascent polypeptide chain (StatPearls, 2023; Wilson, 2014).

03

Biological functions

Protein synthesisTranslationPeptidyl transferase activityPeptide bond formation
04

Disease associations

Infection
05

Safety considerations

Mitochondrial toxicity due to structural similarity between bacterial and mitochondrial ribosomes (Erakovic et al., 2020)Myelosuppression and thrombocytopenia associated with long-term oxazolidinone use (NIH, 2023)Gastrointestinal disturbances and Clostridioides difficile-associated diarrhea (CDC, 2022)Development of antimicrobial resistance through ribosomal modification (Vester & Douthwaite, 2001)
06

Interacting drugs

Erythromycin

10 more in the full profile.

07

Biomarkers

Minimum Inhibitory Concentration (MIC) (CLSI, 2023)Presence of erm resistance genes (PubMed, 2021)Presence of cfr resistance genes (PubMed, 2021)23S rRNA gene mutations (NCBI, 2022)

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