Target intelligence / Profile preview

Mycobacterium tuberculosis 50S ribosomal subunit (Mtb 50S subunit)

Target
Mtb 50S subunit
Molecular classification
Ribonucleoprotein complex, Ribosome
01

Overview

The Mycobacterium tuberculosis 50S ribosomal subunit is the larger component of the bacterial 70S ribosome and is essential for protein biosynthesis (Li et al., 2017, Nature). It consists of the 23S ribosomal RNA (rRNA), the 5S rRNA, and approximately 33 ribosomal proteins that provide the structural framework for translation (Yang et al., 2017, Science). The subunit houses the peptidyl transferase center (PTC), the site where amino acids are enzymatically joined, and the exit tunnel through which the newly formed protein leaves the ribosome (Wilson, 2014, Nature Reviews Microbiology). Because its structure is distinct from the eukaryotic 60S subunit, it serves as a highly effective target for several classes of antibiotics, most notably the oxazolidinones like linezolid. These drugs bind to the 23S rRNA to block the initiation or elongation phases of translation, effectively inhibiting the growth of M. tuberculosis (Poehlsgaard & Douthwaite, 2005, Nature Reviews Microbiology). Understanding the specific architecture of the Mtb 50S subunit is critical for overcoming multi-drug resistant tuberculosis (MDR-TB) through the design of next-generation inhibitors.

Other names
Large ribosomal subunit50S subunit of the M. tuberculosis ribosomeMtb 50S
02

Mechanism of action

Inhibition of bacterial protein synthesis by binding to the 23S rRNA within the peptidyl transferase center (PTC) or the nascent peptide exit tunnel (NPET), which prevents peptide bond formation or the translocation of the growing polypeptide chain (Wilson, 2014, Nature Reviews Microbiology; DrugBank).

03

Biological functions

Protein synthesisTranslationPeptidyl transferase activityPolypeptide exit
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Disease associations

InfectionTuberculosis
05

Safety considerations

Mitochondrial toxicity due to structural similarities between bacterial and human mitochondrial ribosomes (Hashemian et al., 2018, Journal of Antimicrobial Chemotherapy)Myelosuppression including anemia, leukopenia, and thrombocytopeniaPeripheral and optic neuropathy associated with prolonged useRapid emergence of drug resistance in monotherapy settings (WHO)
06

Interacting drugs

Linezolid

9 more in the full profile.

07

Biomarkers

rrl gene mutations (23S rRNA)rplC gene mutations (L3 ribosomal protein)rplD gene mutations (L4 ribosomal protein)Sputum culture conversion

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