thymidine 5'-diphospho-β-D-glucose | 147730-27-6

• 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: thymidine 5'-diphospho-β-D-glucose
• 英文别名: deoxythymidine diphosphate D-glucose；dTDP-D-glucose；Thymidindiphosphat-D-glucose, TDP-D-glucose；[hydroxy-[[(2R,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy]phosphoryl] [(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] hydrogen phosphate
• CAS: 147730-27-6
• 化学式: C₁₆H₂₆N₂O₁₆P₂
• 分子量: 564.334
• InChiKey: YSYKRGRSMLTJNL-JSDFYWKGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.5
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  271
• 氢给体数：
  8
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  thymidine 5'-diphospho-β-D-glucose 在 L-谷氨酸 、 N-(2-hydroxyethyl)piperazine-N'-methanesulfonic acid 、 2,3-dehydratase EvaA 、 3-aminotransferase TcaB₈ 、 4,6-dehydratase RmlB 、 C-3-methyltransferase KijD₁ 、 (S,S)-S-adenosyl-L-methionine 、 甘油 、 sodium chloride 、 magnesium chloride 作用下， 反应 16.0h， 以5%的产率得到thymidine-5'-diphosphate-3-amino-2,3,6-trideoxy-3-C-methyl-D-erythro-hexopyranos-4-ulose
  参考文献：
  名称：

  X-ray Structure of KijD3, a Key Enzyme Involved in the Biosynthesis of d-Kijanose

  摘要：

  D-Kijanose is an unusual nitrosugar found attached to the antibiotic kijanimicin. Ten enzymes are required for its production in Actinomodura kijaniata, a soil-dwelling actinomycete. The focus of this investigation is on the protein encoded by the kijd3 gene and hereafter referred to as KijD3. On the basis of amino acid sequence analyses, KijD3 has been proposed to be an FAD-dependent oxidoreductase, which catalyzes the sixth step in D-kijanose biosynthesis by converting dTDP-3-amino-2,3,6-trideoxy-4-keto-3-methyl-D-glucose into its C-3' nitro derivative. This putative activity, however, has never been demonstrated in vivo or in vitro. Here we report the first structural study of this enzyme. For our investigation, crystals of KijD3 were grown in the presence of dTDP, and the structure was solved to 2.05-angstrom resolution. The enzyme is a tetramer with each subunit folding into three distinct regions: a five a-helical bundle, an eight-stranded beta-sheet, and a second five a-helical bundle. The dTDP moiety is anchored to the protein via the side chains of Glu 113, Gln 254, and Arg 330. The overall fold of KijD3 places it into the well-characterized fatty acyl-CoA dehydrogenase superfamily. There is a decided cleft in each subunit with the appropriate dimensions to accommodate a dTDP-linked sugar. Strikingly, the loop defined by Phe 383 to Ala 388, which projects into the active site, contains two adjacent cis-peptide bonds, Pro 386 and Tyr 387. Activity assays demonstrate that KijD3 requires FAD for activity and that it produces a hydroxylamino product. The molecular architecture of KijD3 described in this report serves as a paradigm for a new family of enzymes that function on dTDP-linked sugar substrates.

  DOI：

  10.1021/bi100318v
• 作为产物：
  描述：

  beta-胸苷 、 蔗糖 在 pyruvate kinase 、 磷烯醇丙酮酸 、 dTMP kinase 、 dTDP kinase 、 thymidine kinase from E_.coli 、 5’-三磷酸腺苷 、 magnesium chloride 、 pyrophosphatase 、 蔗糖磷酸钠 、 dTDP-Glc pyrophosphorylase 作用下， 以 aq. phosphate buffer 为溶剂， 以93 %的产率得到thymidine 5'-diphospho-β-D-glucose
  参考文献：
  名称：

  dTDP 激活的糖核苷酸的系统酶促合成

  摘要：

  在从头和补救生物合成途径的基础上，从容易获得的起始材料成功地大规模制备了多种重要但难以获得的 dTDP 活化糖核苷酸。这种高产合成策略避免了复杂的纯化程序。

  DOI：

  10.1002/anie.202217894

文献信息

• A Novel Method for the Preparation of Nucleoside Diphosphates
  作者：Caren L. Freel Meyers、Richard F. Borch

  DOI：10.1021/ol0167309

  日期：2001.11.1

  [reaction--see text] Sugar nucleoside diphosphates have been prepared using an efficient phosphate coupling reaction that employs a highly reactive zwitterionic phosphoramidate intermediate as the phosphorylating species.

  [反应-见正文]糖核苷二磷酸酯是使用有效的磷酸酯偶联反应制备的，该反应采用高反应性的两性离子氨基磷酸酯中间体作为磷酸化物质。
• X-ray Structure of KijD3, a Key Enzyme Involved in the Biosynthesis of <scp>d</scp>-Kijanose
  作者：Nathan A. Bruender、James B. Thoden、Hazel M. Holden

  DOI：10.1021/bi100318v

  日期：2010.5.4

  D-Kijanose is an unusual nitrosugar found attached to the antibiotic kijanimicin. Ten enzymes are required for its production in Actinomodura kijaniata, a soil-dwelling actinomycete. The focus of this investigation is on the protein encoded by the kijd3 gene and hereafter referred to as KijD3. On the basis of amino acid sequence analyses, KijD3 has been proposed to be an FAD-dependent oxidoreductase, which catalyzes the sixth step in D-kijanose biosynthesis by converting dTDP-3-amino-2,3,6-trideoxy-4-keto-3-methyl-D-glucose into its C-3' nitro derivative. This putative activity, however, has never been demonstrated in vivo or in vitro. Here we report the first structural study of this enzyme. For our investigation, crystals of KijD3 were grown in the presence of dTDP, and the structure was solved to 2.05-angstrom resolution. The enzyme is a tetramer with each subunit folding into three distinct regions: a five a-helical bundle, an eight-stranded beta-sheet, and a second five a-helical bundle. The dTDP moiety is anchored to the protein via the side chains of Glu 113, Gln 254, and Arg 330. The overall fold of KijD3 places it into the well-characterized fatty acyl-CoA dehydrogenase superfamily. There is a decided cleft in each subunit with the appropriate dimensions to accommodate a dTDP-linked sugar. Strikingly, the loop defined by Phe 383 to Ala 388, which projects into the active site, contains two adjacent cis-peptide bonds, Pro 386 and Tyr 387. Activity assays demonstrate that KijD3 requires FAD for activity and that it produces a hydroxylamino product. The molecular architecture of KijD3 described in this report serves as a paradigm for a new family of enzymes that function on dTDP-linked sugar substrates.
• Systematic Enzymatic Synthesis of dTDP‐Activated Sugar Nucleotides
  作者：Fangyu Wei、Rui Yuan、Qin Wen、Liuqing Wen

  DOI：10.1002/anie.202217894

  日期：——

  On the basis of the de novo and salvage biosynthetic pathways, diverse dTDP-activated sugar nucleotides, which are important but difficult to access, were successfully prepared on a large scale from readily available starting materials. This high-yielding synthetic strategy avoids the need for complicated purification procedures.

  在从头和补救生物合成途径的基础上，从容易获得的起始材料成功地大规模制备了多种重要但难以获得的 dTDP 活化糖核苷酸。这种高产合成策略避免了复杂的纯化程序。