Structural highlights
Function
[RFAP_PSEAE] Catalyzes the phosphorylation of heptose(I) of the outer membrane lipopolysaccharide core. The phosphorylation of the lipopolysaccharide core seems to occur prior to translocation to the periplasm and attachment of O-antigen. Also has protein-tyrosine kinase activity: autophosphorylates on all Tyr residues; in vitro can phosphorylate poly(Glu,Tyr).[1] [ACP_ECO45] Carrier of the growing fatty acid chain in fatty acid biosynthesis.[HAMAP-Rule:MF_01217]
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[2]
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
- ↑ 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
