50S ribosomal subunit – 23S ribosomal RNA cryptic site (23S rRNA cryptic site)

The 50S ribosomal subunit – 23S ribosomal RNA cryptic site is a secondary binding pocket for aminoglycoside antibiotics, located within the large ribosomal subunit of bacteria (Sullivan et al., 2018). While aminoglycosides are primarily known for binding to the 16S rRNA of the 30S subunit to interfere with genetic code translation, the discovery of this cryptic site in the 23S rRNA has revealed a dual-action mechanism that contributes significantly to their bactericidal efficacy (Ying et al., 2019). Binding at this site is thought to induce severe translational errors, leading to the production of misfolded or truncated proteins. These aberrant proteins subsequently integrate into the bacterial cell membrane, causing structural damage and increasing permeability, which ultimately results in rapid cell death (Wallace et al., 1973; Borovinskaya et al., 2007). This site is of particular interest in the study of antibiotic resistance, as modifications in the 23S rRNA can influence drug susceptibility. Furthermore, the structural similarity between bacterial 23S rRNA and human mitochondrial rRNA at this site underlies some of the characteristic toxicities associated with aminoglycoside therapy, such as ototoxicity and nephrotoxicity (Waters and Tadi, 2024).

Other names

50S aminoglycoside binding site23S rRNA secondary binding site50S subunit cryptic pocket

Binding to the 23S rRNA cryptic site induces translational errors and promotes the production of misfolded proteins that integrate into and destabilize the bacterial cell membrane.