Target intelligence / Profile preview

Peptidyl transferase center of the 50S ribosomal subunit (PTC)

Target
PTC
Molecular classification
Ribozyme, Ribosomal RNA catalytic center, RNA enzyme, Other (structural region of ribosomal RNA)
01

Overview

The peptidyl transferase center of the 50S ribosomal subunit is a highly conserved ribozyme located within domain V of the 23S ribosomal RNA in prokaryotes (or 28S rRNA in eukaryotes), which plays a crucial catalytic role in protein synthesis by facilitating peptide bond formation between adjacent amino acids during translation and catalyzing peptidyl-tRNA hydrolysis during translation termination[1][2][3][4]. The PTC is composed almost entirely of ribosomal RNA, with minimal direct input from ribosomal proteins in catalysis. It forms the core of the large ribosomal subunit’s active site, engaging with the acceptor ends of A- and P-site tRNAs to correctly orient the reactants[2][3]. Due to its essential and universal function, the PTC is the target of several major classes of antibiotics, which inhibit protein synthesis by binding to this region; resistance mutations in the PTC are clinically significant in the treatment of bacterial infections[4][5]. The importance and evolutionary ancient nature of the PTC also make it a focus of origin-of-life studies[1].

Other names
Peptidyl transferase centerPeptidyl transferase sitePT centerPTC of 23S ribosomal RNA (in prokaryotes)PTC of 28S ribosomal RNA (in eukaryotes)
02

Mechanism of action

Inhibition of peptide bond formation by binding to the PTC; Inhibition of peptide-tRNA release by binding to the PTC; Induction of stalling or misreading during translation by interfering with tRNA positioning; Allosteric modulation of ribosomal activity

03

Biological functions

Catalysis of peptide bond formation during protein synthesisCatalysis of peptidyl-tRNA hydrolysis (peptide release at the end of translation)Central to translation and protein biosynthesis
04

Disease associations

Infection (target for many antibiotics in bacterial infections)Other (potential involvement in resistance mechanisms, especially via mutations conferring resistance to ribosome-targeting drugs)
05

Safety considerations

Toxicity associated with off-target inhibition of mitochondrial ribosomes in eukaryotic cells (notably for chloramphenicol and linezolid)Development of bacterial resistance due to PTC rRNA mutationsPotential for drug-drug interactions with antibiotics acting at the PTC
06

Interacting drugs

Macrolides (e.g., erythromycin)

6 more in the full profile.

07

Biomarkers

Mutations in 23S rRNA (e.g., A2058G, A2059G, C2611T), which confer resistance to macrolide and related antibiotics in bacteria[5]Detection of rRNA methylation patterns

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