UDP-3-O-(3-hydroxymyristoyl)glucosamine N-acyltransferase

From Proteopedia

Function UDP-3-O-(3-hydroxymyristoyl)glucosamine N-acyltransferase or UDP-3-O-acylglucosamine N-acyltransferase (LpxD) is involved in the third step of the biosynthesis of lipid A which is a phosphorylated glycolipid that anchors the lipopolysaccharide to the outer membrane of the cell. Thus, LpxD is essential to survival of Gram-negative bacteria. It catalyzes the N-acylation of UDP-3-O-(3-hydroxytetradeanoyl)glucosamine[1]. LpxD is structurally similar to LpxA which functions as the first enzye in the lipid A biosynthesis. Relevance LpxD inhibitors are antimicrobials[2]. Structural highlights The biological assembly of UDP-3-O-(3-hydroxymyristoyl)glucosamine N-acyltransferase is homotrimer (PDB code 6uec). The 3D structure of LpxD complex with a ligand shows the binding site to be situated at the interface of the crystallographic dimer. There are extensive polar interactions with LpxD as well as hydrogen bonds[3]. Mg coordination site. Water molecules are shown as red spheres.

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3D structures of UDP-3-O-(3-hydroxymyristoyl)glucosamine N-acyltransferase

Updated on 31-January-2021

UDP-3-O-(3-hydroxymyristoyl)glucosamine N-acyltransferase

3pmo, 6ued – PaLpxD – Pseudomonas aeruginosa

4e75, 4e79 – LpxD – Acinetobacter baumannii

3eh0 – EcLpxD – Escherichia coli

2iua – CtLpxD - Chlamydia trachomatis

UDP-3-O-(3-hydroxymyristoyl)glucosamine N-acyltransferase complex

6p83, 6p84, 6p85, 6p86, 6p87, 6p88, 6p89, 6p8a – EcLpxD + inhibitor

6p8b – EcLpxD + peptide inhibitor

4ihf, 4ihg, 4ihh – EcLpxD + ACP

6uec, 6ueg – PaLpxD + inhibitor

2iu8, 2iu9 – CtLpxD + UDP-GlcNAc

References

1. ↑ Bainbridge BW, Karimi-Naser L, Reife R, Blethen F, Ernst RK, Darveau RP. Acyl chain specificity of the acyltransferases LpxA and LpxD and substrate availability contribute to lipid A fatty acid heterogeneity in Porphyromonas gingivalis. J Bacteriol. 2008 Jul;190(13):4549-58. doi: 10.1128/JB.00234-08. Epub 2008 May 2. PMID:18456814 doi:http://dx.doi.org/10.1128/JB.00234-08
2. ↑ Jenkins RJ, Dotson GD. Dual targeting antibacterial peptide inhibitor of early lipid A biosynthesis. ACS Chem Biol. 2012 Jul 20;7(7):1170-7. doi: 10.1021/cb300094a. Epub 2012 Apr 27. PMID:22530734 doi:http://dx.doi.org/10.1021/cb300094a
3. ↑ Kroeck KG, Sacco MD, Smith EW, Zhang X, Shoun D, Akhtar A, Darch SE, Cohen F, Andrews LD, Knox JE, Chen Y. Discovery of dual-activity small-molecule ligands of Pseudomonas aeruginosa LpxA and LpxD using SPR and X-ray crystallography. Sci Rep. 2019 Oct 29;9(1):15450. doi: 10.1038/s41598-019-51844-z. PMID:31664082 doi:http://dx.doi.org/10.1038/s41598-019-51844-z