MurG

MurG is a bacterial glycosyltransferase that plays a central role in peptidoglycan biosynthesis. It catalyzes the transfer of N-acetylglucosamine (GlcNAc) from UDP-GlcNAc to Lipid I, forming Lipid II, the lipid-linked disaccharide-pentapeptide precursor required for cell wall synthesis. This reaction occurs at the cytoplasmic face of the inner bacterial membrane, and MurG is typically a peripheral membrane protein anchored to the inner membrane during catalysis.

Structurally, MurG belongs to the GT-B superfamily of glycosyltransferases and generally adopts a two-domain, Rossmann-like fold that binds both UDP-GlcNAc and the lipid substrate. The catalytic mechanism positions the GlcNAc moiety for transfer to Lipid I, producing Lipid II, which is then flipped across the membrane and elaborated by transglycosylases and transpeptidases into mature peptidoglycan.

Genetically, murG is commonly found within or near the mur operon and is often essential for viability in many bacterial species, including Escherichia coli and various Gram-positive organisms. Disruption of murG typically results in severe defects in cell wall synthesis and compromised growth, though some organisms or conditional mutants can tolerate reduced MurG activity.

MurG is a frequent focus of research on antibiotic targets because blocking Lipid II formation halts peptidoglycan production. Although several inhibitors and substrate analogs have been explored in studies, MurG remains one node within the larger network of enzymes coordinating bacterial cell wall assembly. In model systems, MurG serves as a paradigm for understanding the sequential steps that convert Lipid I to Lipid II in peptidoglycan biosynthesis.