Cytosolic 60S ribosomal subunit A-site (60S A-site) (60S A-site)

The Cytosolic 60S ribosomal subunit A-site (aminoacyl site) is a critical functional region within the large subunit of the eukaryotic 80S ribosome (Source: Molecular Biology of the Cell). It serves as the primary entry point for aminoacyl-tRNA molecules, which carry specific amino acids to be added to the growing polypeptide chain during the elongation phase of translation (Source: Nature Reviews Molecular Cell Biology). The A-site ensures the fidelity of protein synthesis by facilitating the correct pairing between the mRNA codon and the tRNA anticodon. Because protein synthesis is essential for cell survival and proliferation, the 60S A-site is a potent target for various natural toxins and therapeutic agents. For instance, the drug Omacetaxine mepesuccinate (Homoharringtonine) binds to the A-site to inhibit the elongation step of protein synthesis, making it effective in treating Chronic Myeloid Leukemia (Source: FDA Synribo Label). By preventing the binding of aminoacyl-tRNA, these drugs specifically reduce the levels of short-lived proteins like BCR-ABL and MCL-1 that drive cancer progression (Source: Blood Journal). However, because the ribosome is highly conserved across human cells, drugs targeting this site often exhibit significant systemic toxicity, such as severe myelosuppression and gastrointestinal distress (Source: Journal of Clinical Oncology).

Other names

Eukaryotic 60S ribosomal A-siteLarge ribosomal subunit A-siteAminoacyl-tRNA binding site of the 60S subunitRibosomal A-site

Inhibition of protein translation elongation by sterically hindering the binding of aminoacyl-tRNA to the A-site of the 60S ribosomal subunit, thereby preventing the addition of new amino acids to the growing polypeptide chain (Source: PubMed).