murJ

MurJ is an essential inner-membrane protein found in many bacteria, most notably Gram-negative species. It functions as the lipid II flippase, flipping the peptidoglycan precursor lipid II across the cytoplasmic membrane from the cytoplasmic side to the periplasmic side, a critical step in cell wall synthesis. Without MurJ, lipid II cannot reach the site where peptidoglycan is assembled, halting cell wall formation and cell growth.

MurJ is encoded by the murJ gene and is widely conserved among bacteria that synthesize peptidoglycan. It is typically an integral membrane protein predicted to contain multiple transmembrane helices, allowing it to undergo conformational changes required for transport. Structural and biochemical studies have supported an alternating-access mechanism in which MurJ cycles between cytoplasmic- and periplasmic-open states to move lipid II across the membrane. High-resolution structural work and mutational analyses have shed light on key residues and conformational changes involved in substrate binding and translocation.

The lipid II flipping step is central to peptidoglycan biosynthesis, and MurJ’s activity is coordinated with other components of the synthesis pathway. While MurJ is the primary flippase implicated in many bacteria, some research has explored roles for other proteins, such as FtsW, in related pathways of peptidoglycan synthesis, leading to ongoing discussions about the exact division of labor in different organisms and conditions.

From a clinical perspective, MurJ is of interest as a potential target for new antibiotics aiming to disrupt cell wall formation. Small-molecule inhibitors that block MurJ function can impair bacterial growth and sensitize bacteria to other antibiotics, highlighting its relevance in antimicrobial research.