Target intelligence / Profile preview

Bacterial 50S ribosomal subunit 23S rRNA peptide exit tunnel (NPET) (NPET)

Target
NPET
Molecular classification
Other, Ribosomal RNA, Ribonucleoprotein
01

Overview

The bacterial 50S ribosomal subunit 23S rRNA peptide exit tunnel (NPET) is a structural conduit within the large ribosomal subunit through which the nascent polypeptide chain travels as it is synthesized at the peptidyl transferase center. This tunnel is approximately 80-100 Å long and is primarily lined by 23S ribosomal RNA, with structural contributions from ribosomal proteins L4 and L22. It serves as a critical site for antibiotic action; several classes of clinically important antibiotics, most notably macrolides, bind within the tunnel to physically obstruct the elongation of the protein chain. This blockage leads to the premature release of peptidyl-tRNA and the cessation of bacterial protein synthesis. Resistance to these drugs often arises through modifications of the tunnel's lining, such as methylation of the 23S rRNA at position A2058, which prevents drug binding. Understanding the NPET is essential for developing new antimicrobial agents that can overcome existing resistance mechanisms.

Other names
Nascent peptide exit tunnelRibosomal exit tunnel50S exit tunnelNPET
02

Mechanism of action

Inhibition of bacterial protein synthesis by binding to the 23S rRNA within the 50S ribosomal subunit and physically blocking the nascent peptide exit tunnel, which leads to premature dissociation of peptidyl-tRNA and cessation of translation elongation.

03

Biological functions

OtherProtein synthesisTranslation elongationNascent peptide transport
04

Disease associations

Infection
05

Safety considerations

Antibiotic resistanceMitochondrial protein synthesis inhibitionGastrointestinal distressQT prolongationClostridioides difficile infection riskDrug-drug interactions (CYP3A4 inhibition)
06

Interacting drugs

Erythromycin

8 more in the full profile.

07

Biomarkers

23S rRNA A2058 mutationerm methylase genes (ermA, ermB, ermC)cfr methyltransferase gene

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