Target intelligence / Profile preview

Bacterial ribosome 50S subunit peptidyl transferase center (PTC)

Target
PTC
Molecular classification
Ribozyme, Ribosome, Enzyme
01

Overview

The Bacterial ribosome 50S subunit peptidyl transferase center (PTC) is the highly conserved catalytic core of the large ribosomal subunit responsible for synthesizing proteins in bacteria. It functions as a ribozyme, where the 23S ribosomal RNA (rRNA) catalyzes the formation of peptide bonds between the growing polypeptide chain and incoming amino acids (Steitz & Moore, 2003). The PTC is situated at the junction of the ribosomal A- and P-sites and is adjacent to the nascent peptide exit tunnel (NPET). Because of its essentiality for bacterial viability, the PTC is the target for several major classes of antibiotics, including macrolides, oxazolidinones, and lincosamides (Polikanov et al., 2015). These drugs typically bind to the 23S rRNA to physically obstruct the catalytic process or the movement of the nascent peptide. While these therapies are generally selective, the structural similarity between the bacterial PTC and the human mitochondrial ribosome can lead to off-target effects such as bone marrow suppression or lactic acidosis (StatPearls, 2023). Resistance to these drugs often arises through mutations in the 23S rRNA or enzymatic modification of the binding site, such as methylation by Cfr or Erm enzymes (Wilson, 2014).

Other names
Peptidyl transferase center50S peptidyl transferase centerRibosomal peptidyl transferase center23S rRNA peptidyl transferase center
02

Mechanism of action

Inhibition of bacterial protein synthesis by binding to the 23S rRNA within the 50S subunit, which sterically hinders the positioning of aminoacyl-tRNA or blocks the nascent peptide exit tunnel (Wilson, 2014).

03

Biological functions

Protein synthesisPeptide bond formationTranslation elongationPeptidyl-tRNA hydrolysis
04

Disease associations

Infection
05

Safety considerations

Mitochondrial toxicity due to structural homology with human mitochondrial ribosomes (Böttger et al., 2001)MyelosuppressionDevelopment of multidrug resistanceDisruption of the commensal microbiome
06

Interacting drugs

Chloramphenicol

11 more in the full profile.

07

Biomarkers

Minimum Inhibitory Concentration (MIC)23S rRNA mutationsCfr methyltransferase expressionErm-mediated dimethylation

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