isopentenyl thiolodiphosphate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磷酸及其衍生物
• 英文名称: isopentenyl thiolodiphosphate
• 英文别名: isopentyl thiopyrophosphate；3-Methylbut-3-Enylsulfanyl(Phosphonooxy)phosphinic Acid
• 化学式: C₅H₁₂O₆P₂S
• 分子量: 262.16
• InChiKey: YLTQZUVQWVAPNP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  14
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  129
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  S-腺苷-L-蛋氨酸 、 isopentenyl thiolodiphosphate 在 sodium dithionite 、 recombinant viperin from fungal Trichoderma virens 作用下， 以 aq. buffer 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  抗病毒自由基SAM酶viperin的异戊烯基焦磷酸的重构和底物特异性。

  摘要：

  毒蛇毒素是一种自由基SAM酶，已被证明具有对多种病毒的抗病毒活性。但是，其分子机制尚不清楚。我们在此报告，重组真菌和古细菌毒蛇苷酶催化5'-脱氧腺苷基（5'-dA•）加到异戊烯基焦磷酸酯（IPP）的双键上，产生了一种新化合物，我们将其命名为腺苷酸异戊基焦磷酸酯（AIPP） 。该反应对IPP具特异性，因为甲羟戊酸生物合成途径中涉及的其他焦磷酸盐化合物不会与5'-dA反应。采用IPP衍生物作为底物的酶促反应表明，IPP的任何化学变化都会削弱其作为真菌有效底物的能力毒蛇毒。突变研究表明，真菌毒蛋白中Tyr-245侧链上的羟基很可能是自由基添加最后一步中的氢源，从而为真菌毒蛋白催化的自由基反应提供了机理上的见解。蛇毒蛋白与IPP相互作用的基于结构的分子动力学（MD）模拟显示，IPP的异戊烯基基序与蛇毒蛋白的活性位点腔非常吻合，揭示了蛇毒蛋白对IPP的底物特异性的分子基础。总的来说，我们的发现表明I

  DOI：

  10.1074/jbc.ra118.003998
• 作为产物：
  描述：

  3-methyl-3-buten-1-yl thiolophosphate 在 Methanothermobacter thermautotrophicus str. Delta H isopentenyl phosphate kinase 、 5’-三磷酸腺苷 、 2-巯基乙醇 、 magnesium chloride 、 bovine serum albumin 作用下， 生成 isopentenyl thiolodiphosphate
  参考文献：
  名称：

  Characterization of Thermophilic Archaeal Isopentenyl Phosphate Kinases

  摘要：

  Archaea synthesize isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), the essential building blocks of isoprenoid compounds, from mevalonate (MVA). However, an analysis of the genomes of several members of the Archaea failed to identify genes for the enzymes required to convert phosphomevalonate (PM) to IPP In eukaryotes. The recent discovery of an isopentenyl kinase (IPK) in Methanocaldococcus jannaschii (MJ) Suggests a new variation of the MVA pathway where PM is decarboxylated to give isopentenyl phosphate (IP), which is phosphorylated to produce IPP. A blast search using the MJ protein as a probe revealed a subfamily of amino acid kinases that include the fosfomycin resistance protein fomA, which deactivates the antibiotic by phosphorylation of its phosphonate residue in a reaction similar to the conversion of IP to IPP. IPK genes were cloned from two organisms identified in the search, Methanothermobacter thermautotrophicus (MTH) and Thermoplasma acidophilum (THA), and the His-tagged recombinant proteins were purified by Ni-NTA chromatography. The enzymes catalyze the reversible phosphorylation of IP by ATP, K-cq = 6.3 +/- 1. The catalytic efficiencies (V/K) of the proteins were similar to 2 x 10(6) M-1 s(-1). In the reverse direction, ADP wits a substrate inhibitor for THA IPK, K-i(ADP) = 58 +/- 6 mu M, but not for MTH IPK. Both enzymes were active over a broad range of pH and temperature. Five compounds, dimethylallyl phosphate, isopentenyl thiolophosphate, 1-butyl phosphate, 3-buten-1-yl phosphate, and geranyl phosphate, were evaluated as alternative substrates for the MTH and THA IP kinases. All of the compounds were phosphorylated, although the catalytic efficiency was low for geranyl phosphate.

  DOI：

  10.1021/bi9017957

文献信息

• Characterization of Thermophilic Archaeal Isopentenyl Phosphate Kinases
  作者：Mo Chen、C. Dale Poulter

  DOI：10.1021/bi9017957

  日期：2010.1.12

  Archaea synthesize isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), the essential building blocks of isoprenoid compounds, from mevalonate (MVA). However, an analysis of the genomes of several members of the Archaea failed to identify genes for the enzymes required to convert phosphomevalonate (PM) to IPP In eukaryotes. The recent discovery of an isopentenyl kinase (IPK) in Methanocaldococcus jannaschii (MJ) Suggests a new variation of the MVA pathway where PM is decarboxylated to give isopentenyl phosphate (IP), which is phosphorylated to produce IPP. A blast search using the MJ protein as a probe revealed a subfamily of amino acid kinases that include the fosfomycin resistance protein fomA, which deactivates the antibiotic by phosphorylation of its phosphonate residue in a reaction similar to the conversion of IP to IPP. IPK genes were cloned from two organisms identified in the search, Methanothermobacter thermautotrophicus (MTH) and Thermoplasma acidophilum (THA), and the His-tagged recombinant proteins were purified by Ni-NTA chromatography. The enzymes catalyze the reversible phosphorylation of IP by ATP, K-cq = 6.3 +/- 1. The catalytic efficiencies (V/K) of the proteins were similar to 2 x 10(6) M-1 s(-1). In the reverse direction, ADP wits a substrate inhibitor for THA IPK, K-i(ADP) = 58 +/- 6 mu M, but not for MTH IPK. Both enzymes were active over a broad range of pH and temperature. Five compounds, dimethylallyl phosphate, isopentenyl thiolophosphate, 1-butyl phosphate, 3-buten-1-yl phosphate, and geranyl phosphate, were evaluated as alternative substrates for the MTH and THA IP kinases. All of the compounds were phosphorylated, although the catalytic efficiency was low for geranyl phosphate.
• Reconstitution and substrate specificity for isopentenyl pyrophosphate of the antiviral radical SAM enzyme viperin
  作者：Arpita Chakravarti、Kiruthika Selvadurai、Rezvan Shahoei、Hugo Lee、Shirin Fatma、Emad Tajkhorshid、Raven H. Huang

  DOI：10.1074/jbc.ra118.003998

  日期：2018.9

  Viperin is a radical SAM enzyme that has been shown to possess antiviral activity against a broad spectrum of viruses; however, its molecular mechanism is unknown. We report here that recombinant fungal and archaeal viperin enzymes catalyze the addition of the 5'-deoxyadenosyl radical (5'-dA•) to the double bond of isopentenyl pyrophosphate (IPP), producing a new compound we named adenylated isopentyl

  毒蛇毒素是一种自由基SAM酶，已被证明具有对多种病毒的抗病毒活性。但是，其分子机制尚不清楚。我们在此报告，重组真菌和古细菌毒蛇苷酶催化5'-脱氧腺苷基（5'-dA•）加到异戊烯基焦磷酸酯（IPP）的双键上，产生了一种新化合物，我们将其命名为腺苷酸异戊基焦磷酸酯（AIPP） 。该反应对IPP具特异性，因为甲羟戊酸生物合成途径中涉及的其他焦磷酸盐化合物不会与5'-dA反应。采用IPP衍生物作为底物的酶促反应表明，IPP的任何化学变化都会削弱其作为真菌有效底物的能力毒蛇毒。突变研究表明，真菌毒蛋白中Tyr-245侧链上的羟基很可能是自由基添加最后一步中的氢源，从而为真菌毒蛋白催化的自由基反应提供了机理上的见解。蛇毒蛋白与IPP相互作用的基于结构的分子动力学（MD）模拟显示，IPP的异戊烯基基序与蛇毒蛋白的活性位点腔非常吻合，揭示了蛇毒蛋白对IPP的底物特异性的分子基础。总的来说，我们的发现表明I