Cytidine Diphosphoramidate Kinase: An Enzyme Required for the Biosynthesis of the O-Methyl Phosphoramidate Modification in the Capsular Polysaccharides of Campylobacter jejuni

Biochemistry. 2018 Apr 17;57(15):2238-2244. doi: 10.1021/acs.biochem.8b00279. Epub 2018 Apr 3.


Campylobacter jejuni, a leading cause of gastroenteritis, produces a capsular polysaccharide that is derivatized with a unique O-methyl phosphoramidate (MeOPN) modification. This modification contributes to serum resistance and invasion of epithelial cells. Previously, the first three biosynthetic steps for the formation of MeOPN were elucidated. The first step is catalyzed by a novel glutamine kinase (Cj1418), which catalyzes the adenosine triphosphate (ATP)-dependent phosphorylation of the amide nitrogen of l-glutamine. l-Glutamine phosphate is used by cytidine triphosphate (CTP):phosphoglutamine cytidylyltransferase (Cj1416) to displace pyrophosphate from CTP to generate cytidine diphosphate (CDP)-l-glutamine, which is then hydrolyzed by γ-glutamyl-CDP-amidate hydrolase (Cj1417) to form cytidine diphosphoramidate (CDP-NH2). Here, we show that Cj1415 catalyzes the ATP-dependent phosphorylation of CDP-NH2 to form 3'-phospho-cytidine-5'-diphosphoramidate. Cj1415 will also catalyze the phosphorylation of adenosine diphosphoramidate (ADP-NH2) and uridine diphosphoramidate (UDP-NH2) but at significantly reduced rates. It is proposed that Cj1415 be named cytidine diphosphoramidate kinase.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Capsules / genetics
  • Bacterial Capsules / metabolism*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Campylobacter jejuni / genetics
  • Campylobacter jejuni / metabolism*
  • Phosphoric Acids / metabolism*
  • Phosphotransferases / genetics
  • Phosphotransferases / metabolism*
  • Polysaccharides, Bacterial / biosynthesis*
  • Polysaccharides, Bacterial / genetics


  • Bacterial Proteins
  • Phosphoric Acids
  • Polysaccharides, Bacterial
  • Phosphotransferases