uridine diphospho N-acetylglucosamine | 1067638-64-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 英文名称: uridine diphospho N-acetylglucosamine
• 英文别名: CDP-GlcNAc；UDP-GlcNAc；[(2R,3R,4R,5S,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl] [[(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] hydrogen phosphate
• CAS: 1067638-64-5
• 化学式: C₁₇H₂₈N₄O₁₆P₂
• 分子量: 606.374
• InChiKey: RHRPMGQZMVYSNV-CFRASDGPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -7
• 重原子数：
  39
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  310
• 氢给体数：
  9
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  磷烯醇丙酮酸 、 uridine diphospho N-acetylglucosamine 在 MurA from Escherichia Coli 作用下， 以 phosphate buffer 为溶剂， 生成
  参考文献：
  名称：

  MurA 和 AroA 的四面体（α-羧基缩酮磷酸盐）中间体的非酶促分解，两种羧乙烯基转移酶。不同官能团的质子化控制着分解的速度和命运

  摘要：

  检查了羧乙烯基转移酶 MurA 和 AroA 的四面体中间体 (THI) 的非酶促分解机制，以阐明 THI 的固有反应性与用于促进催化的酶促策略之间的相互作用。THI 降解是通过磷酸盐离开和 CO 键断裂。它是酸催化的，取决于 α-羧基缩酮磷酸盐官能团的羧基的质子化状态，MurA 和 AroA THI 的电离分别为 pK(a) = 3.2 +/- 0.1 和 4.3 +/- 0.1。在 pL 2.0 下 MurA THI 的溶剂氘动力学同位素效应为 1.3 +/- 0.4，与一般酸催化一致。pK(a) 表明通过磷酸桥氧的质子化进行分子内一般酸催化，尽管 H(3)O(+) 催化也是可能的。产物分布随pH变化。在所有 pH 值下，尤其是低 pH 值下，主要的分解产物是丙酮酸 + 磷酸盐 + R-OH（R-OH = UDP-GlcNAc 或莽草酸 3-磷酸盐）。在较高的 pH 值下，观察到缩酮比

  DOI：

  10.1021/ja0349655
• 作为产物：
  描述：

  N-acetylglucosamine-1-phosphate 、 胞苷-5’-三磷酸 在 yeast inorganic pyrophosphatase 、 N-acetylglucosamine-1-phosphate pyrophosphorylase from C_. jejuni NCTC 11168 、 三羟甲基氨基甲烷盐酸盐 、 magnesium chloride 作用下， 反应 2.0h， 以64.6%的产率得到uridine diphospho N-acetylglucosamine
  参考文献：
  名称：

  A chemoenzymatic route to synthesize unnatural sugar nucleotides using a novel N-acetylglucosamine-1-phosphate pyrophosphorylase from Camphylobacter jejuni NCTC 11168

  摘要：

  A novel N-acetylglucosamine-1-phosphate pyrophosphorylase was identified from Campylobacter jejuni NCTC 11168. An unprecedented degree of substrate promiscuity has been revealed by systematic studies on its substrate specificities towards sugar-1-P and NTP. The yields of the synthetic reaction of seven kinds of sugar nucleotides catalyzed by the enzyme were up to 60%. In addition, the yields of the other nine were around 20%. With this enzyme, three novel sugar nucleotide analogs were synthesized on a preparative scale and well characterized. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.06.003

文献信息

• Systematic study on the broad nucleotide triphosphate specificity of the pyrophosphorylase domain of the N-acetylglucosamine-1-phosphate uridyltransferase from Escherichia coli K12
  作者：Junqiang Fang、Wanyi Guan、Li Cai、Guofeng Gu、Xianwei Liu、Peng George Wang

  DOI：10.1016/j.bmcl.2009.09.039

  日期：2009.11

  N-Acetylglucosamine-1-phosphate uridyltransferase (GlmU) from Escherichia coli K12 is a bifunctional enzyme that catalyzes both the acetyltransfer and uridyltransfer reactions in the prokaryotic UDP-GlcNAc biosynthetic pathway. In this study, we report the broad substrate specificity of the pyrophosphorylase domain of GlmU during its uridyltransfer reaction and the substrate priority is ranked in the following order: UTP > dUTP > dTTP >> CTP > dATP/dm(6) ATP. This pyrophosphorylase domain of GlmU is also a tool to synthesize UDP-GlcNAc analogs, two examples of which were synthesized herein in multiple mg scale in vitro. (C) 2009 Elsevier Ltd. All rights reserved.
• Probing the roles of conserved residues in uridyltransferase domain of Escherichia coli K12 GlmU by site-directed mutagenesis
  作者：Shuaishuai Wang、Xuan Fu、Yunpeng Liu、Xian-wei Liu、Lin Wang、Junqiang Fang、Peng George Wang

  DOI：10.1016/j.carres.2015.05.007

  日期：2015.9

  N-Acetylglucosamine-1-phosphate uridyltransferase (GlmU) is a bifunctional enzyme that catalyzes both acetyltransfer and uridyltransfer reactions in the prokaryotic UDP-GlcNAc biosynthesis pathway. Our previous study demonstrated that the uridyltransferase domain of GlmU (tGlmU) exhibited a flexible substrate specificity, which could be further applied in unnatural sugar nucleotides preparation. However, the structural basis of tolerating variant substrates is still not clear. Herein, we further investigated the roles of several highly conserved amino acid residues involved in substrate binding and recognition by structure-and sequence-guided site-directed mutagenesis. Out of total 16 mutants designed, tGlmU Q76E mutant which had a novel catalytic activity to convert CTP and GlcNAc-1P into unnatural sugar nucleotide CDP-GlcNAc was identified. Furthermore, tGlmU Y103F and N169R mutants were also investigated to have enhanced uridyltransferase activities compared with wide-type tGlmU. (C) 2015 Elsevier Ltd. All rights reserved.
• A chemoenzymatic route to synthesize unnatural sugar nucleotides using a novel N-acetylglucosamine-1-phosphate pyrophosphorylase from Camphylobacter jejuni NCTC 11168
  作者：Junqiang Fang、Mengyang Xue、Guofeng Gu、Xian-wei Liu、Peng George Wang

  DOI：10.1016/j.bmcl.2013.06.003

  日期：2013.8

  A novel N-acetylglucosamine-1-phosphate pyrophosphorylase was identified from Campylobacter jejuni NCTC 11168. An unprecedented degree of substrate promiscuity has been revealed by systematic studies on its substrate specificities towards sugar-1-P and NTP. The yields of the synthetic reaction of seven kinds of sugar nucleotides catalyzed by the enzyme were up to 60%. In addition, the yields of the other nine were around 20%. With this enzyme, three novel sugar nucleotide analogs were synthesized on a preparative scale and well characterized. (C) 2013 Elsevier Ltd. All rights reserved.
• Nonenzymatic Breakdown of the Tetrahedral (α-Carboxyketal Phosphate) Intermediates of MurA and AroA, Two Carboxyvinyl Transferases. Protonation of Different Functional Groups Controls the Rate and Fate of Breakdown
  作者：Bartosz Byczynski、Shehadeh Mizyed、Paul J. Berti

  DOI：10.1021/ja0349655

  日期：2003.10.1

  alpha-carboxyketal phosphate functionality, with ionizations at pK(a) = 3.2 +/- 0.1 and 4.3 +/- 0.1 for MurA and AroA THIs, respectively. The solvent deuterium kinetic isotope effect for MurA THI at pL 2.0 was 1.3 +/- 0.4, consistent with general acid catalysis. The pK(a)'s suggested intramolecular general acid catalysis through protonation of the bridging oxygen of the phosphate, though H(3)O(+) catalysis was also

  检查了羧乙烯基转移酶 MurA 和 AroA 的四面体中间体 (THI) 的非酶促分解机制，以阐明 THI 的固有反应性与用于促进催化的酶促策略之间的相互作用。THI 降解是通过磷酸盐离开和 CO 键断裂。它是酸催化的，取决于 α-羧基缩酮磷酸盐官能团的羧基的质子化状态，MurA 和 AroA THI 的电离分别为 pK(a) = 3.2 +/- 0.1 和 4.3 +/- 0.1。在 pL 2.0 下 MurA THI 的溶剂氘动力学同位素效应为 1.3 +/- 0.4，与一般酸催化一致。pK(a) 表明通过磷酸桥氧的质子化进行分子内一般酸催化，尽管 H(3)O(+) 催化也是可能的。产物分布随pH变化。在所有 pH 值下，尤其是低 pH 值下，主要的分解产物是丙酮酸 + 磷酸盐 + R-OH（R-OH = UDP-GlcNAc 或莽草酸 3-磷酸盐）。在较高的 pH 值下，观察到缩酮比