Related Experiment Video

Updated: Feb 28, 2026

Following Cell-fate in E. coli After Infection by Phage Lambda
06:10

Following Cell-fate in E. coli After Infection by Phage Lambda

Published on: October 14, 2011

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Convergent MurJ flippase inhibition by phage lysis proteins

Yancheng E Li1, S Francesca Antillon2,3, Grace F Baron1

  • 1Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA.

Nature
|February 25, 2026
PubMed

Insights

Antimicrobial drug resistance requires new targets. Phage proteins called single-gene lysis proteins (Sgls) inhibit the essential MurJ bacterial enzyme, offering a novel drug design strategy against Gram-negative bacteria.

Area of Science:

  • Microbiology
  • Structural Biology
  • Drug Discovery

Background:

  • Antimicrobial drug resistance is a critical global health issue.
  • The bacterial lipid II flippase MurJ is a key target for new antibiotics.
  • Single-gene lysis proteins (Sgls) from phages M and PP7 are the only known inhibitors of Gram-negative MurJ.

Purpose of the Study:

  • To elucidate the common mechanism of MurJ inhibition by phage-encoded Sgls.
  • To identify and characterize novel Sgl inhibitors of MurJ.
  • To reveal a potential pathway for designing new antimicrobial drugs.

Main Methods:

  • Determined the structures of MurJ-bound SglM and SglPP7.
  • Identified and structurally characterized a third MurJ-targeting Sgl, SglCJ3.
  • Comparative structural analysis of Sgl-MurJ interactions.

Main Results:

  • SglM, SglPP7, and SglCJ3 share a common mechanism for inhibiting MurJ.
  • These Sgls convergently evolved to bind MurJ at a conserved interface.
  • The inhibition mechanism involves trapping MurJ in a periplasm-open conformation.

Conclusions:

  • Phage Sgls provide a conserved inhibitory mechanism against the essential bacterial MurJ.
  • The structural insights into Sgl-MurJ interactions reveal a promising avenue for antimicrobial drug design.
  • Convergent evolution offers a framework for developing novel inhibitors targeting bacterial cell wall biosynthesis.

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