riboflavin adenine dinucleotide

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 黄素核苷酸
• 英文名称: riboflavin adenine dinucleotide
• 英文别名: flavin adenine dinucleotide；flavinadenine dinucleotide；FAD2+；FAD；[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl] [(2R,3S,4S)-5-(7,8-dimethyl-2,4-dioxobenzo[g]pteridin-10-yl)-2,3,4-trihydroxypentyl] phosphate
• 化学式: C₂₇H₃₁N₉O₁₅P₂
• 分子量: 783.542
• InChiKey: VWWQXMAJTJZDQX-UYBVJOGSSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  -5.1
• 重原子数：
  53
• 可旋转键数：
  13
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  362
• 氢给体数：
  7
• 氢受体数：
  20

反应信息

• 作为反应物：
  描述：

  氯甲基甲硫醚 、 riboflavin adenine dinucleotide 在 sodium dithionite 、 sodium phosphate 作用下， 生成
  参考文献：
  名称：

  合成催化辅酶中间体的酶活化：黄酮酶对核苷酸的甲基化作用

  摘要：

  为了促进功能性酶的产生并研究其机理，尤其是在复杂的辅酶依赖性系统中，用催化活性辅酶中间体激活无活性载脂酶制剂是一种有吸引力的策略。黄素-亚甲基亚胺化合物的简单化学合成就说明了这一点，该化合物以前被提议为参与核酸代谢的几种重要黄素酶催化循环的关键中间体。黄素依赖性RNA甲基转移酶和胸苷酸合酶脱辅基蛋白都可以用这种合成化合物进行重组，从而在各自的转移RNA和dUMP底物中产生了C5-尿嘧啶甲基化的活性酶。该策略有望在酶学中普遍应用。

  DOI：

  10.1002/anie.201706219
• 作为产物：
  描述：

  维生素 B2 在 sodium dithionite 、 recombinant human FAD synthetase transcript variant 2 、 recombinant human flavokinase 、 sodium fluoride 、 5’-三磷酸腺苷 、 magnesium chloride 作用下， 生成 riboflavin adenine dinucleotide
  参考文献：
  名称：

  The antibiotics roseoflavin and 8-demethyl-8-amino-riboflavin from Streptomyces davawensis are metabolized by human flavokinase and human FAD synthetase

  摘要：

  The non-pathogenic Gram-positive soil bacterium Streptomyces davawensis synthesizes the riboflavin (vitamin B-2) analogs roseoflavin (RoF) and 8-demethyl-8-amino-riboflavin (AF). Both compounds are antibiotics. Notably, a number of other riboflavin analogs are currently under investigation with regard to the development of novel antiinfectives. As a first step towards understanding the metabolism of riboflavin analogs in humans, the key enzymes flavokinase (EC 2.7.1.26) and FAD synthetase (EC 2.7.7.2) were studied. Human flavokinase efficiently converted RoF and AF to roseoflavin mononucleotide (RoFMN) and 8-demethyl-8-amino-riboflavin mononucleotide (AFMN), respectively. Human FAD synthetase accepted RoFMN but not AFMN as a substrate. Consequently, roseoflavin adenine dinucleotide (RoFAD) was synthesized by the latter enzyme but not 8-demethyl-8-amino-riboflavin adenine dinucleotide (AFAD). The cofactor analogs RoFMN, AFMN and RoFAD have different physicochemical properties as compared to FMN and FAD. Thus, the cofactor analogs have the potential to render flavoenzymes inactive, which may negatively affect human metabolism. RoF, but not AF, was found to inhibit human flavokinase. In summary, we suggest that AF has a lower toxic potential and may be better suited as a lead structure to develop antimicrobial compounds. (C) 2011 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2011.08.029
• 作为试剂：
  描述：

  松属素 在 flavin reductase enzyme from E_. Coli 、 radicicol halogenase from Chaetomium chiversii D₄₅₆E/T₅₀₁S mutant 、 NADH 、 riboflavin adenine dinucleotide 、 magnesium chloride 作用下， 以 aq. phosphate buffer 、 乙醇 为溶剂， 反应 2.0h， 以15%的产率得到
  参考文献：
  名称：

  RadH：一种用于整合到合成途径中的多功能卤素酶。

  摘要：

  黄素依赖性卤化酶是用于提供具有改进的生物活性的卤化分子或用于合成衍生化的中间体的有用酶。我们展示了如何使用真菌卤化酶 RadH 对一系列生物活性芳香族支架进行区域选择性卤化。RadH 的定点诱变用于识别催化残基并提供对真菌卤化酶机制的深入了解。还开发了一种高通量荧光筛选，使 RadH 突变体能够进化并具有改进的特性。最后，我们展示了如何结合来自真菌、细菌和植物的生物合成基因来编码一种新途径，从而在大肠杆菌中产生一种新型氯化香豆素“非天然”产物。

  DOI：

  10.1002/anie.201706342

文献信息

• Enzyme Activation with a Synthetic Catalytic Co‐enzyme Intermediate: Nucleotide Methylation by Flavoenzymes
  作者：Charles Bou‐Nader、David Cornu、Vincent Guerineau、Thibault Fogeron、Marc Fontecave、Djemel Hamdane

  DOI：10.1002/anie.201706219

  日期：2017.10.2

  catalytically competent coenzyme intermediate is an attractive strategy. This is illustrated with the simple chemical synthesis of a flavin‐methylene iminium compound previously proposed as a key intermediate in the catalytic cycle of several important flavoenzymes involved in nucleic acid metabolism. Reconstitution of both flavin‐dependent RNA methyltransferase and thymidylate synthase apoproteins with this

  为了促进功能性酶的产生并研究其机理，尤其是在复杂的辅酶依赖性系统中，用催化活性辅酶中间体激活无活性载脂酶制剂是一种有吸引力的策略。黄素-亚甲基亚胺化合物的简单化学合成就说明了这一点，该化合物以前被提议为参与核酸代谢的几种重要黄素酶催化循环的关键中间体。黄素依赖性RNA甲基转移酶和胸苷酸合酶脱辅基蛋白都可以用这种合成化合物进行重组，从而在各自的转移RNA和dUMP底物中产生了C5-尿嘧啶甲基化的活性酶。该策略有望在酶学中普遍应用。
• The antibiotics roseoflavin and 8-demethyl-8-amino-riboflavin from Streptomyces davawensis are metabolized by human flavokinase and human FAD synthetase
  作者：Danielle B. Pedrolli、Shinobu Nakanishi、Maria Barile、Madina Mansurova、Eleonora C. Carmona、Andreas Lux、Wolfgang Gärtner、Matthias Mack

  DOI：10.1016/j.bcp.2011.08.029

  日期：2011.12

  The non-pathogenic Gram-positive soil bacterium Streptomyces davawensis synthesizes the riboflavin (vitamin B-2) analogs roseoflavin (RoF) and 8-demethyl-8-amino-riboflavin (AF). Both compounds are antibiotics. Notably, a number of other riboflavin analogs are currently under investigation with regard to the development of novel antiinfectives. As a first step towards understanding the metabolism of riboflavin analogs in humans, the key enzymes flavokinase (EC 2.7.1.26) and FAD synthetase (EC 2.7.7.2) were studied. Human flavokinase efficiently converted RoF and AF to roseoflavin mononucleotide (RoFMN) and 8-demethyl-8-amino-riboflavin mononucleotide (AFMN), respectively. Human FAD synthetase accepted RoFMN but not AFMN as a substrate. Consequently, roseoflavin adenine dinucleotide (RoFAD) was synthesized by the latter enzyme but not 8-demethyl-8-amino-riboflavin adenine dinucleotide (AFAD). The cofactor analogs RoFMN, AFMN and RoFAD have different physicochemical properties as compared to FMN and FAD. Thus, the cofactor analogs have the potential to render flavoenzymes inactive, which may negatively affect human metabolism. RoF, but not AF, was found to inhibit human flavokinase. In summary, we suggest that AF has a lower toxic potential and may be better suited as a lead structure to develop antimicrobial compounds. (C) 2011 Elsevier Inc. All rights reserved.