Convergent MurJ flippase inhibition by phage lysis proteins - PubMed
3 hours ago
- #Phage lysis proteins
- #MurJ flippase
- #Antimicrobial resistance
- Antimicrobial drug resistance is a global health challenge requiring new targets.
- MurJ, an essential lipid II flippase, is a promising but underexplored antimicrobial target.
- Single-gene lysis proteins (Sgls) from phages M (SglM) and PP7 (SglPP7) inhibit Gram-negative MurJ.
- SglM and SglPP7 share no sequence similarity but inhibit MurJ through a common mechanism.
- Structures of MurJ-bound SglM and SglPP7 reveal a periplasm-open conformation trapping mechanism.
- A third distinct Sgl from phage Changjiang3 (SglCJ3) also targets MurJ similarly.
- Convergent evolution of Sgls suggests a pathway for drug design targeting MurJ.