6-amino-6-deoxyfutalosine

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 5'-脱氧核糖核苷
• 英文名称: 6-amino-6-deoxyfutalosine
• 英文别名: 6-aminodeoxyfutalosine；aminofutalosine；AFL；Aminodeoxyfutalosine；3-[3-[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]propanoyl]benzoic acid
• 化学式: C₁₉H₁₉N₅O₆
• 分子量: 413.39
• InChiKey: JSTYUEOJPRFLHR-SCFUHWHPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  174
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  6-amino-6-deoxyfutalosine 在 aminofutalosine glycosidase, MqnB 作用下， 以 aq. buffer 为溶剂， 反应 3.0h， 生成 dehypoxanthinylfutalosine
  参考文献：
  名称：

  Menaquinone Biosynthesis: Formation of Aminofutalosine Requires a Unique Radical SAM Enzyme

  摘要：

  Menaquinone (MK, vitamin K-2) is a lipid-soluble molecule that participates in the bacterial electron transport chain. In mammalian cells, MK functions as an essential vitamin for the activation of various proteins involved in blood clotting and bone metabolism. Recently, a new pathway for the biosynthesis of this cofactor was discovered in Streptomyces coelicolor A3(2) in which chorismate is converted to aminofutalosine in a reaction catalyzed by MqnA and an unidentified enzyme. Here, we reconstitute the biosynthesis of aminofutalosine and demonstrate that the missing enzyme (aminofutalosine synthase, MqnE) is a radical SAM enzyme that catalyzes the addition of the adenosyl radical to the double bond of 3-[(1-carboxyvinyl)oxy]benzoic acid. This is a new reaction type in the radical SAM superfamily.

  DOI：

  10.1021/ja408594p
• 作为产物：
  描述：

  methyl m-enolpyruvylbenzoate 在 sodium dithionite 、 aminofutalosine synthase mqnE 、 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 10.0h， 生成 6-amino-6-deoxyfutalosine
  参考文献：
  名称：

  Menaquinone Biosynthesis: Formation of Aminofutalosine Requires a Unique Radical SAM Enzyme

  摘要：

  Menaquinone (MK, vitamin K-2) is a lipid-soluble molecule that participates in the bacterial electron transport chain. In mammalian cells, MK functions as an essential vitamin for the activation of various proteins involved in blood clotting and bone metabolism. Recently, a new pathway for the biosynthesis of this cofactor was discovered in Streptomyces coelicolor A3(2) in which chorismate is converted to aminofutalosine in a reaction catalyzed by MqnA and an unidentified enzyme. Here, we reconstitute the biosynthesis of aminofutalosine and demonstrate that the missing enzyme (aminofutalosine synthase, MqnE) is a radical SAM enzyme that catalyzes the addition of the adenosyl radical to the double bond of 3-[(1-carboxyvinyl)oxy]benzoic acid. This is a new reaction type in the radical SAM superfamily.

  DOI：

  10.1021/ja408594p

文献信息

• Deamination of 6-Aminodeoxyfutalosine in Menaquinone Biosynthesis by Distantly Related Enzymes
  作者：Alissa M. Goble、Rafael Toro、Xu Li、Argentina Ornelas、Hao Fan、Subramaniam Eswaramoorthy、Yury Patskovsky、Brandan Hillerich、Ron Seidel、Andrej Sali、Brian K. Shoichet、Steven C. Almo、Subramanyam Swaminathan、Martin E. Tanner、Frank M. Raushel

  DOI：10.1021/bi400750a

  日期：2013.9.17

  Proteins of unknown function belonging to cog1816 and cog0402 were characterized. Sav2595 from Steptomyces avermitilis MA-4680, Ace10264 from Acidothermus cellulolyticus 11B, Nis0429 from Nitratiruptor sp. SB155-2 and Dr0824 from Deinococcus radiodurans R1 were cloned, purified, and their substrate profiles determined. These enzymes were previously incorrectly annotated as adenosine deaminases or chlorohydrolases. It was shown here that these enzymes actually deaminate 6-aminodeoxyfutalosine. The deamination of 6-aminodeoxyfutalosine is part of an alternative menaquinone biosynthetic pathway that involves the formation of futalosine. 6-Aminodeoxyfutalosine is deaminated by these enzymes with catalytic efficiencies greater than 106 M-1 s(-1), Km values of 0.9-6.0 mu M, and k(cat) values of 1.2-8.6 Adenosine, 2'-deoxyadenosine, thiomethyladenosine, and S-adenosylhomocysteine are deaminated at least an order of magnitude slower than 6-aminodeoxyfutalosine. The crystal structure of Nis0429 was determined and the substrate, 6-aminodeoxyfutalosine, was positioned in the active site on the basis of the presence of adventitiously bound benzoic acid. In this model, Ser-145 interacts with the carboxylate moiety of the substrate. The structure of.Dr0824 was also determined, but a collapsed active site pocket prevented docking of substrates. A computational model of Sav2595 was built on the basis of the crystal structure of adenosine deaminase and substrates were docked. The model predicted a conserved arginine after beta-strand 1 to be partially responsible for the substrate specificity of Sav2595.
• Menaquinone Biosynthesis: Formation of Aminofutalosine Requires a Unique Radical SAM Enzyme
  作者：Nilkamal Mahanta、Dmytro Fedoseyenko、Tohru Dairi、Tadhg P. Begley

  DOI：10.1021/ja408594p

  日期：2013.10.16

  Menaquinone (MK, vitamin K-2) is a lipid-soluble molecule that participates in the bacterial electron transport chain. In mammalian cells, MK functions as an essential vitamin for the activation of various proteins involved in blood clotting and bone metabolism. Recently, a new pathway for the biosynthesis of this cofactor was discovered in Streptomyces coelicolor A3(2) in which chorismate is converted to aminofutalosine in a reaction catalyzed by MqnA and an unidentified enzyme. Here, we reconstitute the biosynthesis of aminofutalosine and demonstrate that the missing enzyme (aminofutalosine synthase, MqnE) is a radical SAM enzyme that catalyzes the addition of the adenosyl radical to the double bond of 3-[(1-carboxyvinyl)oxy]benzoic acid. This is a new reaction type in the radical SAM superfamily.