2-Hexaprenyl-6-hydroxyphenol

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 2-Hexaprenyl-6-hydroxyphenol
• 英文别名: 3-[(2E,6E,10E,14E,18E)-3,7,11,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaenyl]benzene-1,2-diol
• 化学式: C₃₆H₅₄O₂
• 分子量: 518.8
• InChiKey: LXZAKEGPNJYZBT-LSRIWWPWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.4
• 重原子数：
  38
• 可旋转键数：
  17
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-Hexaprenyl-6-hydroxyphenol 、 S-腺苷蛋氨酸 生成 2-Hexaprenyl-6-methoxyphenol 、 氢(+1)阳离子 、 S-(5'-腺苷)-L-高半胱氨酸
  参考文献：
  名称：

  酵母和大鼠Coq3和大肠杆菌UbiG多肽催化辅酶Q生物合成中的两个O-甲基转移酶步骤。

  摘要：

  泛醌（辅酶Q或Q）是一种脂质，在真核生物的线粒体内膜和原核生物的质膜的电子传输链中起作用。酿酒酵母的Q缺陷突变体在八个COQ基因（coq1-coq8）之一中存在缺陷，无法在不可发酵的碳源上生长。Q的生物合成涉及两个单独的O-甲基化步骤。在酵母中，第一次O-甲基化利用3，4-二羟基-5-六聚戊二烯基苯甲酸作为底物，并被认为是由Coq3p催化的，Coq3p是一种32.7-kDa的蛋白质，与大肠杆菌O-甲基转移酶UbiG的同源性为40％ 。在这项研究中，已经化学合成了对应于第二个O-甲基化步骤的法呢基化类似物demethyl-Q（3）和Q（3），并用于体外研究酵母线粒体中的Q生物合成。酵母和大鼠Coq3p都将脱甲基Q（3）前体识别为底物。另外，纯化了大肠杆菌UbiGp并发现其催化了两个O-甲基化步骤。此外，使用针对酵母Coq3p的抗体来确定Coq3多肽与酵母线粒体内膜的基质侧外围相关。结果表明，

  DOI：

  10.1074/jbc.274.31.21665

文献信息

• Structural insights into the methyl donor recognition model of a novel membrane-binding protein UbiG
  作者：Yuwei Zhu、Xuguang Jiang、Chongyuan Wang、Yang Liu、Xiaojiao Fan、Linjuan Zhang、Liwen Niu、Maikun Teng、Xu Li

  DOI：10.1038/srep23147

  日期：——

  UbiG is a SAM-dependent O-methyltransferase, catalyzing two O-methyl transfer steps for ubiquinone biosynthesis in Escherichia coli. UbiG possesses a unique sequence insertion between β4 and α10, which is used for membrane lipid interaction. Interestingly, this sequence insertion also covers the methyl donor binding pocket. Thus, the relationship between membrane binding and entrance of the methyl donor of UbiG during the O-methyl transfer process is a question that deserves further exploration. In this study, we reveal that the membrane-binding region of UbiG gates the entrance of methyl donor. When bound with liposome, UbiG displays an enhanced binding ability toward the methyl donor product S-adenosylhomocysteine. We further employ protein engineering strategies to design UbiG mutants by truncating the membrane interacting region or making it more flexible. The ITC results show that the binding affinity of these mutants to SAH increases significantly compared with that of the wild-type UbiG. Moreover, we determine the structure of UbiG∆^165–187 in complex with SAH. Collectively, our results provide a new angle to cognize the relationship between membrane binding and entrance of the methyl donor of UbiG, which is of benefit for better understanding the O-methyl transfer process for ubiquinone biosynthesis.

  UbiG是一种依赖于SAM的O-甲基转移酶，在大肠杆菌中催化泛醌生物合成的两个O-甲基转移步骤。UbiG在β4和α10之间具有独特的序列插入，用于与膜脂互作用。有趣的是，这个序列插入也覆盖了甲基供体结合口袋。因此，UbiG的膜结合和甲基供体进入O-甲基转移过程之间的关系是一个值得进一步探索的问题。在这项研究中，我们揭示了UbiG的膜结合区域门控甲基供体的进入。当与脂质体结合时，UbiG对甲基供体产物S-腺苷基高半胱氨酸表现出增强的结合能力。我们进一步采用蛋白工程策略设计UbiG突变体，通过截断膜相互作用区域或使其更加灵活。ITC结果显示，与野生型UbiG相比，这些突变体对SAH的结合亲和力显著增加。此外，我们确定了UbiG∆^165–187与SAH复合物的结构。总的来说，我们的结果提供了一种新的角度来认识UbiG的膜结合和甲基供体进入之间的关系，这有助于更好地理解泛醌生物合成的O-甲基转移过程。

• Complementation of <i>coq3</i> Mutant Yeast by Mitochondrial Targeting of the <i>Escherichia coli</i> UbiG Polypeptide:  Evidence That UbiG Catalyzes Both <i>O</i>-Methylation Steps in Ubiquinone Biosynthesis
  作者：Adam Y. Hsu、Wayne W. Poon、Jennifer A. Shepherd、David C. Myles、Catherine F. Clarke

  DOI：10.1021/bi9602932

  日期：1996.1.1

  Ubiquinone functions in the mitochondrial electron transport chain, Recent evidence suggests that the reduced form of ubiquinone (ubiquinol) may also function as a lipid soluble antioxidant. The biosynthesis of ubiquinone requires two O-methylation steps. In eukaryotes, the first O-methylation step is carried out by the Coq3 polypeptide, which catalyzes the transfer of a methyl group from S-adenosylmethionine to 3,4-dihydroxy-5-polyprenylbenzoate. In Escherichia coli, 2-polyprenyl-6-hydroxyphenol is the predicted substrate; however, the corresponding O-methyltransferase has not been identified. The second O-methylation step in E. coli, the conversion of demethylubiquinone to ubiquinone, is carried out by the UbiG methyltransferase, which is 40% identical in amino acid sequence with the yeast Coq3 methyltransferase. On the basis of the chemical similarity of the first and last methyl-acceptor substrates and the high degree of amino acid sequence identity between Coq3p and UbiG, the ability of UbiG to catalyze both O-methylation steps was investigated. The current study shows that the ubiG gene is able to restore respiration in the yeast coq3 mutant, provided ubiG; is modified to contain a mitochondrial leader sequence. The mitochondrial targeting of O-methyltransferase activity is an essential feature of the ability to restore respiration and hence ubiquinone biosynthesis in vivo. In vitro import assays show the mitochondrial leader sequence present on Coq3p functions to direct mitochondrial import of Coq3p in vitro and that processing to the mature form requires a membrane potential. In vitro methyltransferase assays with E. coli cell lysates and synthetically prepared farnesylated-substrate analogs indicate that UbiG methylates both the derivative of the eukaryotic intermediate, 3,4-dihydroxy-5-farnesylbenzoate, as well as that of the E. coli intermediate, 2-farnesyl-6-hydroxyphenol. The data presented indicate that the yeast Coq3 polypeptide is located in the mitochondria and that E. coli UbiG catalyzes both O-methylation steps in E. coli.