LpxD

LpxD is a bacterial N-acyltransferase involved in the biosynthesis of lipid A, the membrane-anchoring moiety of lipopolysaccharide found in Gram-negative bacteria. Encoded by the lpxD gene, the enzyme catalyzes the transfer of a (R)-3-hydroxyacyl chain from acyl carrier protein (ACP) to the 2-amino group of UDP-3-O-(acyl)-glucosamine, producing UDP-2,3-diacylglucosamine. This reaction follows those catalyzed by LpxA and LpxC and is an early, essential step in lipid A assembly.

Structurally, LpxD belongs to the left-handed beta-helix (LβH) family of acyltransferases. Crystal structures from multiple species show a repeating beta-helix core that organizes the active site and a substrate-binding groove that accommodates acyl-ACP and the UDP-linked sugar. The enzyme’s specificity for acyl chain length and hydroxylation state helps determine the final lipid A acylation pattern, which influences membrane properties and host immune recognition.

LpxD is conserved across many Gram-negative bacteria and is generally essential for viability because of its role in outer membrane biogenesis. Because lipid A synthesis is unique to Gram-negative organisms and required for pathogenicity in some species, LpxD and other enzymes in the pathway have been investigated as potential targets for new antibacterial agents. Structural and biochemical studies continue to inform efforts to modulate its activity.