| Structural highlights
Function
WAAP_PSEAE Kinase involved in the biosynthesis of the core oligosaccharide region of lipopolysaccharide (LPS) (PubMed:11741974, PubMed:21810964, PubMed:30237436). Catalyzes the phosphorylation of heptose I (HepI), the first heptose added to the Kdo2-lipid A module (PubMed:11741974). Also has protein-tyrosine kinase activity: autophosphorylates on all Tyr residues; in vitro can phosphorylate poly(Glu,Tyr) (PubMed:11741974).[1] [2] [3]
Publication Abstract from PubMed
Phosphorylation of Pseudomonas aeruginosa lipopolysaccharide (LPS) is important for maintaining outer membrane integrity and intrinsic antibiotic resistance. We solved the crystal structure of the LPS heptose kinase WaaP, which is essential for growth of P. aeruginosa. WaaP was structurally similar to eukaryotic protein kinases and, intriguingly, was complexed with acylated-acyl carrier protein (acyl-ACP). WaaP produced by in vitro transcription-translation was insoluble unless acyl-ACP was present. WaaP variants designed to perturb the acyl-ACP interaction were less stable in cells and exhibited reduced kinase function. Mass spectrometry identified myristyl-ACP as the likely physiological binding partner for WaaP in P. aeruginosa. Together, these results demonstrate that acyl-ACP is required for WaaP protein solubility and kinase function. To the best of our knowledge, this is the first report describing acyl-ACP in the role of a cofactor necessary for the production and stability of a protein partner.
Acylated-acyl carrier protein stabilizes the Pseudomonas aeruginosa WaaP lipopolysaccharide heptose kinase.,Kreamer NNK, Chopra R, Caughlan RE, Fabbro D, Fang E, Gee P, Hunt I, Li M, Leon BC, Muller L, Vash B, Woods AL, Stams T, Dean CR, Uehara T Sci Rep. 2018 Sep 20;8(1):14124. doi: 10.1038/s41598-018-32379-1. PMID:30237436[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Zhao X, Lam JS. WaaP of Pseudomonas aeruginosa is a novel eukaryotic type protein-tyrosine kinase as well as a sugar kinase essential for the biosynthesis of core lipopolysaccharide. J Biol Chem. 2002 Feb 15;277(7):4722-30. doi: 10.1074/jbc.M107803200. Epub 2001, Dec 11. PMID:11741974 doi:http://dx.doi.org/10.1074/jbc.M107803200
- ↑ Delucia AM, Six DA, Caughlan RE, Gee P, Hunt I, Lam JS, Dean CR. Lipopolysaccharide (LPS) inner-core phosphates are required for complete LPS synthesis and transport to the outer membrane in Pseudomonas aeruginosa PAO1. mBio. 2011 Aug 2;2(4):e00142-11. PMID:21810964 doi:10.1128/mBio.00142-11
- ↑ Kreamer NNK, Chopra R, Caughlan RE, Fabbro D, Fang E, Gee P, Hunt I, Li M, Leon BC, Muller L, Vash B, Woods AL, Stams T, Dean CR, Uehara T. Acylated-acyl carrier protein stabilizes the Pseudomonas aeruginosa WaaP lipopolysaccharide heptose kinase. Sci Rep. 2018 Sep 20;8(1):14124. doi: 10.1038/s41598-018-32379-1. PMID:30237436 doi:http://dx.doi.org/10.1038/s41598-018-32379-1
- ↑ Kreamer NNK, Chopra R, Caughlan RE, Fabbro D, Fang E, Gee P, Hunt I, Li M, Leon BC, Muller L, Vash B, Woods AL, Stams T, Dean CR, Uehara T. Acylated-acyl carrier protein stabilizes the Pseudomonas aeruginosa WaaP lipopolysaccharide heptose kinase. Sci Rep. 2018 Sep 20;8(1):14124. doi: 10.1038/s41598-018-32379-1. PMID:30237436 doi:http://dx.doi.org/10.1038/s41598-018-32379-1
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