Structure and reactivity of LpxD, the N -acyltransferase of lipid A biosynthesis

• DOI: 10.1073/pnas.0606356104
• Publication Date: 2007-03-06T01:44:34Z
• Authors: Lori Buetow; Terry K. Smith; Alice Dawson; Stewart Fyffe; William N. Hunter
• Keywords: Acyltransferases; Transferase; Ternary complex

The external layer of the Gram-negative bacterial outer membrane is primarily composed a protective, selectively permeable LPS. biosynthesis LPS relies on UDP-3-O-acyl-glucosamine N-acyltransferase (LpxD), which transfers 3-hydroxy-arachidic acid from acyl carrier protein to 2' amine UDP-3-O-myristoyl glucosamine in Chlamydia trachomatis. Our crystallographic study reveals that LpxD homotrimer, each subunit constructed novel combination an N-terminal uridine-binding domain, core lipid-binding and C-terminal helical extension. Highly conserved residues dominate nucleotide binding. Phe-43 Tyr-49 form pi-stacking interactions with uracil, Asn-46 His-284 hydrogen bonds phosphate groups. These place moiety at catalytic center formed by two adjacent subunits. Here His-247 contribute mechanism involving nucleophilic attack one substrate carbonyl carbon thioester conjugate. Serendipitously, our fatty (FA) binding groove near center. MS elucidated presence FA mixture LpxD, palmitic most prevalent. placement UDP-N-acetylglucosamine provides details ligand allows for description structure reactivity early stage assembly.