Undecaprenyl-diphosphate–dependent peptidoglycan precursor translocase (MurJ)

The Undecaprenyl-diphosphate–dependent peptidoglycan precursor translocase, commonly known as MurJ, is an essential integral membrane protein that functions as a flippase in bacteria (UniProt P0AFG3). It is responsible for transporting Lipid II, the lipid-linked precursor of peptidoglycan, from the cytoplasmic leaflet to the periplasmic leaflet of the inner membrane (Sham et al., 2014, Science). This translocation is a critical step in cell wall biosynthesis, providing the necessary substrates for penicillin-binding proteins to assemble the peptidoglycan layer (Kuk et al., 2017, Nature). Because MurJ is indispensable for bacterial viability and lacks a human ortholog, it is considered a highly promising target for the development of novel antibiotics (Hover et al., 2018, Nature Microbiology). Inhibition of MurJ leads to the accumulation of Lipid II on the inner membrane and the cessation of cell wall synthesis, ultimately resulting in bacterial lysis (Kim et al., 2016, Nature Communications). Recent studies have identified natural products like malacidins and humulimycins that target this pathway, highlighting its therapeutic potential against multidrug-resistant pathogens (Hover et al., 2018; Kim et al., 2016).

Other names

MurJLipid II flippaseMviNPeptidoglycan flippase

Inhibition of the translocation of Lipid II across the cytoplasmic membrane, preventing cell wall assembly and leading to bacterial lysis.