Substrate Specificity and Chemical Mechanism for the Reaction Catalyzed by Glutamine Kinase

Biochemistry
Zane W TaylorFrank M Raushel

Abstract

Campylobacter jejuni, a leading cause of gastroenteritis worldwide, has a unique O-methyl phosphoramidate (MeOPN) moiety attached to its capsular polysaccharide. Investigations into the biological role of MeOPN have revealed that it contributes to the pathogenicity of C. jejuni, and this modification is important for the colonization of C. jejuni. Previously, the reactions catalyzed by four enzymes (Cj1418-Cj1415) from C. jejuni that are required for the biosynthesis of the phosphoramidate modification have been elucidated. Cj1418 (l-glutamine kinase) catalyzes the formation of the initial phosphoramidate bond with the ATP-dependent phosphorylation of the amide nitrogen of l-glutamine. Here we show that Cj1418 catalyzes the phosphorylation of l-glutamine through a three-step reaction mechanism via the formation of covalent pyrophosphorylated ( Enz-X-Pβ-Pγ) and phosphorylated ( Enz-X-Pβ) intermediates. In the absence of l-glutamine, the enzyme was shown to catalyze a positional isotope exchange (PIX) reaction within β-[18O4]-ATP in support of the formation of the Enz-X-Pβ-Pγintermediate. In the absence of ATP, the enzyme was shown to catalyze a molecular isotope exchange (MIX) reaction between l-glutamine phosphate and [15N-amid...Continue Reading

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Oct 13, 2017·Biochemistry·Zane W TaylorFrank M Raushel

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Citations

Mar 3, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Janusz J PetkowskiSara Seager
Dec 24, 2019·Chemical Reviews·Jason B Hedges, Katherine S Ryan

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Campylobacteriosis is caused by the bacteria Campylobacter jejuni and is a common cause of gastroenteritis in humans. Discover the latest research on Campylobacteriosis here.