20026-02-25 カリフォルニア工科大学（Caltech）
Three distinct phage Sgl proteins lock the flippase MurJ in an outward-facing state, providing a template for antibiotic discovery.Credit: Juliet Lee
＜関連情報＞
- https://www.caltech.edu/about/news/finding-new-ways-to-kill-bacteria-new-insights-into-the-transporter-murj
- https://www.nature.com/articles/s41586-026-10163-w
ファージ溶解タンパク質による収束的MurJフリッパーゼ阻害 Convergent MurJ flippase inhibition by phage lysis proteins
Yancheng E. Li (李妍成),S. Francesca Antillon,Grace F. Baron,Karthik Chamakura,Ry Young & William M. Clemons Jr
Nature Published:25 February 2026
DOI:https://doi.org/10.1038/s41586-026-10163-w
Abstract
Antimicrobial drug resistance poses a global health challenge that necessitates the identification of new druggable targets1,2,3. The essential lipid II flippase MurJ is a promising yet underexplored antimicrobial target in bacterial cell wall biosynthesis4,5,6,7. The only known inhibitors of Gram-negative (diderm) MurJ are the single-gene lysis proteins (Sgls) from the lytic single-strand RNA phages M (SglM) and PP7 (SglPP7)8,9. SglM and SglPP7 have distinct evolutionary origins and share no sequence similarity. Here we describe a common mechanism of MurJ inhibition by these phage-encoded Sgls. We determined the structures of MurJ-bound SglM and SglPP7 and discovered a third distinct MurJ-targeting Sgl from the predicted phage Changjiang3 (SglCJ3) that we also characterized structurally. Our findings demonstrate that all three Sgls evolved convergently to trap MurJ in a periplasm-open conformation through a common MurJ interface, revealing a pathway for drug design.
