Quinupristin

Quinupristin is a streptogramin B antibiotic that acts by binding to the 50S ribosomal subunit and blocking the nascent peptide exit tunnel. Quinupristin binds to 23S rRNA through an extensive network of hydrophobic interactions and hydrogen bonds involving nucleotides from domain II, IV and V. The binding site of quinupristin is located at the entrance to the ribosomal tunnel and does not contact the active site of the 50S subunit. Quinupristin occupies the same space as the macrolides, which is consistent with the strong competition observed between erythromycin and streptogramin B. The synergistic effect with dalfopristin derives from direct hydrophobic interactions between both compounds and shared contacts with a single nucleotide, A2062.
Upon binding of the streptogramins, the peptidyl transferase centre undergoes a significant conformational transition, leading to a stable, non-productive orientation of the universally conserved U2585. Mutations of this rRNA base are known to yield dominant lethal phenotypes, indicating that the conformational change within the peptidyl transferase centre is mainly responsible for the bactericidal activity of the streptogramins.

Fig. 1 Interactions of streptogramins with 23S rRNA. (Harms J M.; et al. 2004)