5-amino-5-(4-hydroxybenzyl)-6-(D-ribitylimino)-5,6-dihydrouracil

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-amino-5-(4-hydroxybenzyl)-6-(D-ribitylimino)-5,6-dihydrouracil
• 英文别名: 5-amino-5-[(4-hydroxyphenyl)methyl]-6-[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]imino-1,3-diazinane-2,4-dione
• 化学式: C₁₆H₂₂N₄O₇
• 分子量: 382.37
• InChiKey: XETIGMNRSOUDLK-USDBNLMRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.5
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  198
• 氢给体数：
  8
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5-amino-5-(4-hydroxybenzyl)-6-(D-ribitylimino)-5,6-dihydrouracil 、 S-腺苷蛋氨酸 生成 脱氧腺嘌呤核苷 、 7,8-didemethyl-8-hydroxy-5-deazariboflavin 、 氢(+1)阳离子 、 L-蛋氨酸 、 铵
  参考文献：
  名称：

  Biosynthesis of F₀, Precursor of the F₄₂₀ Cofactor, Requires a Unique Two Radical-SAM Domain Enzyme and Tyrosine as Substrate

  摘要：

  Cofactors play key roles in metabolic pathways. Among them F-420 has proved to be a very attractive target for the selective inhibition of archaea and actinobacteria. Its biosynthesis, in a unique manner, involves a key enzyme, F-0-synthase. This enzyme is a large monomer in actinobacteria, while it is constituted of two subunits in archaea and cyanobacteria. We report here the purification of both types of F-0-synthase and their in vitro activities. Our study allows us to establish that F-0-synthase, from both types, uses 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione and tyrosine as substrates but not 4-hydroxylphenylpyruvate as previously suggested. Furthermore, our data support the fact that F-0-synthase generates two 5'-deoxyadenosyl radicals for catalysis which is unprecedented in reaction catalyzed by radical SAM enzymes.

  DOI：

  10.1021/ja307762b
• 作为产物：
  描述：

  5-氨基-6-核糖基氨基-2,4-(1H,3H)嘧啶二酮 、 L-酪氨酸 、 S-腺苷蛋氨酸 生成 亚氨基甘氨酸 、 脱氧腺嘌呤核苷 、 5-amino-5-(4-hydroxybenzyl)-6-(D-ribitylimino)-5,6-dihydrouracil 、 氢(+1)阳离子 、 L-蛋氨酸
  参考文献：
  名称：

  Biosynthesis of F₀, Precursor of the F₄₂₀ Cofactor, Requires a Unique Two Radical-SAM Domain Enzyme and Tyrosine as Substrate

  摘要：

  Cofactors play key roles in metabolic pathways. Among them F-420 has proved to be a very attractive target for the selective inhibition of archaea and actinobacteria. Its biosynthesis, in a unique manner, involves a key enzyme, F-0-synthase. This enzyme is a large monomer in actinobacteria, while it is constituted of two subunits in archaea and cyanobacteria. We report here the purification of both types of F-0-synthase and their in vitro activities. Our study allows us to establish that F-0-synthase, from both types, uses 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione and tyrosine as substrates but not 4-hydroxylphenylpyruvate as previously suggested. Furthermore, our data support the fact that F-0-synthase generates two 5'-deoxyadenosyl radicals for catalysis which is unprecedented in reaction catalyzed by radical SAM enzymes.

  DOI：

  10.1021/ja307762b

文献信息

• Biosynthetic Versatility and Coordinated Action of 5′-Deoxyadenosyl Radicals in Deazaflavin Biosynthesis
  作者：Benjamin Philmus、Laure Decamps、Olivier Berteau、Tadhg P. Begley

  DOI：10.1021/ja513287k

  日期：2015.4.29

  Coenzyme F-420 is a redox cofactor found in methanogens and in various actinobacteria. Despite the major biological importance of this cofactor, the biosynthesis of its deazaflavin core (8-hydroxy-5-deazaflavin, F-o) is still poorly understood. F-o synthase, the enzyme involved, is an unusual multidomain radical SAM enzyme that uses two separate 5'-deoxyadenosyl radicals to catalyze F-o formation. In this paper, we report a detailed mechanistic study on this complex enzyme that led us to identify (1) the hydrogen atoms abstracted from the substrate by the two radical SAM domains, (2) the second tyrosine-derived product, (3) the reaction product of the CofH-catalyzed reaction, (4) the demonstration that this product is a substrate for CofG, and (5) a stereochemical study that is consistent with the formation of a p-hydroxybenzyl radical at the CofH active site. These results enable us to propose a mechanism for F-o synthase and uncover a new catalytic motif in radical SAM enzymology involving the use of two 5'-deoxyadenosyl radicals to mediate the formation of a complex heterocycle.