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

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Cytidine Diphosphoramidate Kinase: An Enzyme Required for the Biosynthesis of the O-Methyl Phosphoramidate Modification in the Capsular Polysaccharides of Campylobacter jejuni
Biochemistry ( IF 2.9 ) Pub Date : 2018-03-26 00:00:00 , DOI: 10.1021/acs.biochem.8b00279
Zane W. Taylor ₁ , Frank M. Raushel _{1,

2}

Affiliation

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.

中文翻译：

胞苷二磷酸氨基甲酸酯激酶：空肠弯曲杆菌荚膜多糖中O-甲基磷酸氨基甲酸酯修饰的生物合成所需的酶。

空肠弯曲杆菌是肠胃炎的主要原因，它产生的荚膜多糖经独特的O-甲基氨基磷酸酯（MeOPN）修饰而衍生。这种修饰有助于血清抗性和上皮细胞的侵袭。以前，已经阐明了形成MeOPN的前三个生物合成步骤。第一步是由新型谷氨酰胺激酶（Cj1418）催化，它催化1-谷氨酰胺酰胺氮的三磷酸腺苷（ATP）依赖性磷酸化。升谷氨酰胺磷酸盐所使用的三磷酸胞苷（CTP）：phosphoglutamine胞苷酰转移酶（Cj1416）来置换从焦磷酸CTP，以生成二磷酸胞苷（CDP） -升-谷氨酰胺，然后由γ-谷氨酰基-CDP-氨基甲酸酯水解酶（Cj1417）水解，形成胞苷二磷酸氨基甲酸酯（CDP-NH ₂）。在这里，我们显示Cj1415催化CDP-NH ₂的ATP依赖性磷酸化，形成3'-磷酸-胞苷-5'-二磷酸氨基甲酸酯。Cj1415还可以催化腺苷二磷酸氨基磷酸酯（ADP-NH ₂）和尿苷二磷酸氨基磷酸酯（UDP-NH ₂）的磷酸化，但是速率明显降低。提议将Cj1415命名为胞苷二磷酸酰胺酸激酶。

更新日期：2018-03-26

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