Target intelligence / Profile preview

Bacterial 70S ribosome 30S subunit A-site (30S A-site) (30S A-site)

Target
30S A-site
Molecular classification
Ribonucleoprotein complex, Ribosomal RNA, Translation machinery
01

Overview

The bacterial 70S ribosome 30S subunit A-site, also known as the aminoacyl-tRNA binding site or decoding center, is a fundamental component of the bacterial translation apparatus (Schmeing & Ramakrishnan, 2009, Nature). It is primarily composed of highly conserved sequences within the 16S ribosomal RNA (rRNA), specifically helix 44, which facilitates the high-fidelity selection of aminoacyl-tRNAs based on mRNA codons (Vicens & Westhof, 2003, ChemBioChem). This site is the primary pharmacological target for several classes of broad-spectrum antibiotics used to treat bacterial infections. Aminoglycosides, such as gentamicin and amikacin, bind directly to the A-site, causing a conformational change that reduces the accuracy of the decoding process, leading to the synthesis of mistranslated, dysfunctional proteins (Magnet & Blanchard, 2005, Chem. Rev.). Tetracyclines also target this region by sterically hindering the binding of aminoacyl-tRNA to the A-site, thereby halting protein synthesis (Chopra & Roberts, 2001, Microbiol. Mol. Biol. Rev.). While these drugs are effective against a wide range of pathogens, their use is often limited by safety concerns such as nephrotoxicity and ototoxicity, which can occur due to structural similarities between bacterial and human mitochondrial ribosomes (Guthrie, 2008, Semin. Hear.).

Other names
Aminoacyl-tRNA binding site16S rRNA A-siteDecoding center30S decoding site
02

Mechanism of action

Aminoglycosides bind to the 16S rRNA A-site to induce mRNA misreading and translocation inhibition (Magnet & Blanchard, 2005, Chem. Rev.); Tetracyclines sterically block the A-site to prevent aminoacyl-tRNA binding (Chopra & Roberts, 2001, Microbiol. Mol. Biol. Rev.).

03

Biological functions

Protein synthesismRNA decodingTranslation elongation
04

Disease associations

Bacterial infection
05

Safety considerations

NephrotoxicityOtotoxicityNeuromuscular blockadeAntibiotic resistanceMitochondrial toxicity
06

Interacting drugs

Gentamicin

10 more in the full profile.

07

Biomarkers

Minimum Inhibitory Concentration (MIC)16S rRNA gene mutations (e.g., A1408G)Aminoglycoside-modifying enzymes (AMEs)

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