Target intelligence / Profile preview

A-site on 16S ribosomal RNA of the bacterial 30S ribosomal subunit (16S rRNA A-site)

Target
16S rRNA A-site
Molecular classification
Ribosomal RNA (rRNA), RNA component of ribonucleoprotein complex (30S ribosome), Other (non-coding RNA structural site)
01

Overview

The A-site on 16S ribosomal RNA of the bacterial 30S ribosomal subunit is a highly conserved, functionally crucial region within the small subunit of the prokaryotic ribosome responsible for the accurate decoding of mRNA via codon-anticodon interactions. The 16S rRNA itself is the main RNA component of the 30S subunit and serves as a scaffold for ribosomal proteins, but the A-site is specifically where incoming aminoacyl-tRNA is selected and paired with the mRNA codon. Key nucleotides within the site—G530, A1492, and A1493—undergo conformational changes that ensure high fidelity in tRNA selection and prevent incorporation of incorrect amino acids. This site is a primary therapeutic target for several antibiotics, notably aminoglycosides and tetracyclines, which interfere with bacterial protein synthesis by binding to the A-site, thereby inducing misreading of mRNA or blocking tRNA entry, respectively. Due to its essential role, mutations at the A-site are associated with antibiotic resistance and may serve as molecular biomarkers. As an RNA structural target, it is distinct from classical proteinaceous drug targets and represents a key node in the central dogma of molecular biology and infectious disease therapy.

Other names
Aminoacyl-tRNA binding site on 16S rRNADecoding site of 16S rRNA30S ribosomal A-site
02

Mechanism of action

Aminoglycosides bind to the A-site, distorting its structure, inducing misreading of mRNA and inhibiting protein synthesis. Tetracyclines block the binding of aminoacyl-tRNA to the A-site, inhibiting translation.

03

Biological functions

Translation fidelity through codon-anticodon recognitionAminoacyl-tRNA selection and accommodation during protein synthesisStructural scaffolding for ribosomal proteinsInteraction with mRNA for decoding genetic information
04

Disease associations

Infection (therapeutic target for antibiotics)Antibiotic resistance through mutation in this site
05

Safety considerations

Off-target effects may impact mitochondrial ribosomes (similar structure to bacteria), leading to toxicityResistance may arise due to point mutations in the A-site nucleotides
06

Interacting drugs

Aminoglycosides

1 more in the full profile.

07

Biomarkers

Specific mutations in 16S rRNA associated with aminoglycoside and tetracycline resistance (e.g., changes at A1492, A1493, and G530)

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