Alternate binding cleft on the bacterial 30S ribosomal subunit

The alternate binding cleft on the bacterial 30S ribosomal subunit is a secondary interaction site for aminoglycoside antibiotics, such as paromomycin, identified through molecular dynamics and Brownian dynamics simulations (Dlugosz and Trylska, 2009). While the primary target of aminoglycosides is the aminoacyl-tRNA (A-site) decoding center on the 16S rRNA, this alternate cleft provides an additional binding region that is hypothesized to play a crucial role in the inhibition of the translocation step of protein synthesis (Dlugosz and Trylska, 2009). Located in the niche between the head and the shoulder of the 30S subunit, near intersubunit bridges B6 and B8, this site is explored by drugs as they diffuse toward their primary binding sites (Dlugosz and Trylska, 2009). Binding at this alternate cleft may interfere with the conformational dynamics and rotation of the 30S head, which are essential for the movement of the mRNA-tRNA complex during translocation (Dlugosz and Trylska, 2009). The discovery of this site suggests that the mechanism of action for aminoglycosides is multi-modal, involving both decoding interference and translocation inhibition through multiple binding events (Louzoun Zada et al., 2020). This site represents a potential target for the development of new antimicrobial agents designed to specifically disrupt ribosomal translocation and overcome resistance associated with A-site mutations (Dlugosz and Trylska, 2009).

Other names

Alternate cleft siteSecondary paromomycin binding site30S translocation inhibition cleftAlternate binding pocket

Inhibition of the translocation step of protein synthesis by binding to a secondary cleft on the 30S ribosomal subunit, potentially interfering with the movement of the mRNA-tRNA complex.