In molecular biology, UDP-3-O-N-acetylglucosamine deacetylase (also known as UDP-3-O-[3-hydroxymyristoyl] N-acetylglucosamine deacetylase or UDP-3-O-acyl-GlcNAc deacetylase), , is a bacterial enzyme involved in lipid A biosynthesis.
It is a zinc-dependent metalloamidase that catalyses the second and committed step in the biosynthesis of lipid A. Lipid A anchors lipopolysaccharide (the major constituent of the outer membrane) into the membrane in Gram negative bacteria. It shows no homology to mammalian metalloamidases and is essential for cell , making it an important target for the development of novel antibacterial compounds. The structure of UDP-3-O-N-acetylglucosamine deacetylase (LpxC) from Aquifex aeolicus has a two-layer alpha/beta structure similar to that of the second domain of ribosomal protein S5, only in LpxC there is a duplication giving two structural repeats of this fold, each repeat being elaborated with additional structures forming the active site. LpxC contains a zinc-binding motif, which resides at the base of an active site cleft and adjacent to a hydrophobic tunnel occupied by a fatty acid. This tunnel accounts for the specificity of LpxC toward substrates and inhibitors bearing appropriately positioned 3-O-fatty acid substituents.