Structure and Mechanism of the Lipid Flippase MurJ.

Journal Article (Journal Article;Review)

Biosynthesis of many important polysaccharides (including peptidoglycan, lipopolysaccharide, and N-linked glycans) necessitates the transport of lipid-linked oligosaccharides (LLO) across membranes from their cytosolic site of synthesis to their sites of utilization. Much of our current understanding of LLO transport comes from genetic, biochemical, and structural studies of the multidrug/oligosaccharidyl-lipid/polysaccharide (MOP) superfamily protein MurJ, which flips the peptidoglycan precursor lipid II. MurJ plays a pivotal role in bacterial cell wall synthesis and is an emerging antibiotic target. Here, we review the mechanism of LLO flipping by MurJ, including the structural basis for lipid II flipping and ion coupling. We then discuss inhibition of MurJ by antibacterials, including humimycins and the phage M lysis protein, as well as how studies on MurJ could provide insight into other flippases, both within and beyond the MOP superfamily.

Full Text

Duke Authors

Cited Authors

  • Kuk, ACY; Hao, A; Lee, S-Y

Published Date

  • June 21, 2022

Published In

Volume / Issue

  • 91 /

Start / End Page

  • 705 - 729

PubMed ID

  • 35320686

Electronic International Standard Serial Number (EISSN)

  • 1545-4509

Digital Object Identifier (DOI)

  • 10.1146/annurev-biochem-040320-105145


  • eng

Conference Location

  • United States