2IU9

Chlamydia trachomatis LpxD with 100mM UDPGlcNAc (Complex II)

Summary for 2IU9

• Entry DOI: 10.2210/pdb2iu9/pdb
• Related: 2IU8 2IUA
• Descriptor: UDP-3-O-[3-HYDROXYMYRISTOYL] GLUCOSAMINE N-ACYLTRANSFERASE, BETA-MERCAPTOETHANOL, SULFATE ION, ... (6 entities in total)
• Functional Keywords: transferase, udp-3- o-acyl-glucosamine n-acyltransferase, acyltransferase, lipid a biosynthesis, left-handed beta helix, complex with udpglcnac, enzyme, homotrimer, lipid synthesis
• Biological source: CHLAMYDIA TRACHOMATIS
• Total number of polymer chains: 3
• Total formula weight: 124526.49

Authors

Buetow, L.,Smith, T.K.,Dawson, A.,Fyffe, S.,Hunter, W.N. (deposition date: 2006-05-30, release date: 2007-02-20, Last modification date: 2023-12-13)

Primary citation

Buetow, L.,Smith, T.K.,Dawson, A.,Fyffe, S.,Hunter, W.N.
Structure and Reactivity of Lpxd, the N-Acyltransferase of Lipid a Biosynthesis
Proc.Natl.Acad.Sci.USA, 104:4321-, 2007

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

PubMed: 17360522
DOI: 10.1073/PNAS.0606356104

Experimental method

X-RAY DIFFRACTION (3.1 Å)