MurJ-lipid II flippase complex (MurJ)

The MurJ-lipid II flippase complex is a critical component of the bacterial cell wall synthesis machinery. MurJ is an essential integral membrane protein that belongs to the multidrug and toxic compound extrusion (MATE)-like family and serves as the primary flippase for Lipid II, the lipid-linked precursor of peptidoglycan (Kuk et al., 2017, Nature). It facilitates the transport of Lipid II from the inner to the outer leaflet of the cytoplasmic membrane, a rate-limiting step in cell wall assembly driven by the proton motive force. Because MurJ is essential for the survival of both Gram-positive and Gram-negative bacteria and lacks a human homolog, it is a highly attractive target for novel antibiotic development (Chu et al., 2016, Nature Chemical Biology). Disrupting the interaction between MurJ and Lipid II or inhibiting the flippase activity leads to the depletion of periplasmic peptidoglycan precursors, resulting in severe cell wall defects and rapid bacterial lysis. Recent structural studies have elucidated the inward-to-outward conformational changes required for transport, providing a basis for the structure-based drug design of inhibitors like humimycins.

Other names

Lipid II flippaseMviNPeptidoglycan flippaseMurJ flippaseMurJ-Lipid II complex

Inhibition of the translocation of Lipid II from the cytoplasmic to the periplasmic leaflet of the inner membrane, which prevents the polymerization of the peptidoglycan layer and leads to bacterial cell lysis (Sham et al., 2014, Science).