3-O-geranylgeranyl sn-glycerol-1-phosphate

• 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: 3-O-geranylgeranyl sn-glycerol-1-phosphate
• 英文别名: GGGP；sn-3-O-(geranylgeranyl)glycerol 1-phosphate(2-)；[(2S)-2-hydroxy-3-[(2E,6E,10E)-3,7,11,15-tetramethylhexadeca-2,6,10,14-tetraenoxy]propyl] phosphate
• 化学式: C₂₃H₃₉O₆P
• 分子量: 442.533
• InChiKey: BJLPWUCPFAJINB-UAQSTNRTSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  30
• 可旋转键数：
  15
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  geranylgeranyl diphosphate 、 3-O-geranylgeranyl sn-glycerol-1-phosphate 生成 2,3-bis-O-geranylgeranyl sn-glycerol-1-phosphate 、 pyrophosphoric acid
  参考文献：
  名称：

  （S）-2,3-Di-O-geranylgeranylglyceryl磷酸合酶，来自嗜热古细菌Sulfolobus solfataricus。膜内源异戊二烯基转移酶的分子克隆和表征，涉及古细菌醚连接的膜脂质的生物合成。

  摘要：

  古细菌的膜脂的核心结构具有一些独特的特性，可以使古细菌与其他细菌，真核生物区别开来。（S）-2,3-二-O-香叶基香叶酸甘油酯磷酸合酶催化古兰基香叶基基团从香叶基香叶基二磷酸酯向（S）-3-O-香叶基香叶酸甘油酯磷酸酯的转移，参与古细菌膜脂质的生物合成。众所周知，在呼吸醌，血红素，叶绿素，维生素E和紫草素的生物合成中，UbiA异戊二烯基转移酶家族的酶催化异戊二烯基向具有疏水环结构的各种受体的转移。发现嗜热古细菌Sulfolobus solfataricus在其基因组中编码UbiA异戊二烯基转移酶的三个同源物。由SSO0583编码的同系物之一在大肠杆菌中表达，纯化和鉴定。放射分析和质谱分析数据表明该酶特异性催化（S）-2，3-二-O-香叶基香叶基甘油基磷酸酯的生物合成。该酶的直向同源物几乎在所有古细菌基因组中都编码，这一事实清楚地表明了其功能的重要性。使用UbiA异戊二烯基转移酶家族的一些典型成员的氨基酸序列及其来自S

  DOI：

  10.1074/jbc.m409207200
• 作为产物：
  描述：

  isopentenyl pyrophosphate 在 3-O-geranylgeranyl sn-glycerol-1-phosphate synthase 、 magnesium 、 geranylgeranyl diphosphate synthase 作用下， 反应 1.0h， 生成 3-O-geranylgeranyl sn-glycerol-1-phosphate
  参考文献：
  名称：

  Identification of CDP-Archaeol Synthase, a Missing Link of Ether Lipid Biosynthesis in Archaea

  摘要：

  Archaeal membrane lipid composition is distinct from Bacteria and Eukarya, consisting of isoprenoid chains etherified to the glycerol carbons. Biosynthesis of these lipids is poorly understood. Here we identify and characterize the archaeal membrane protein CDP-archaeol synthase (CarS) that catalyzes the transfer of the nucleotide to its specific archaeal lipid substrate, leading to the formation of a CDP-activated precursor (CDP-archaeol) to which polar head groups are attached. The discovery of CarS enabled reconstitution of the entire archaeal lipid biosynthesis pathway in vitro, starting from simple isoprenoid building blocks and using a set of five purified enzymes. The cell free synthetic strategy for archaeal lipids we describe opens opportunity for studies of archaeal lipid biochemistry. Additionally, insights into archaeal lipid biosynthesis reported here allow addressing the evolutionary hypothesis of the lipid divide between Archaea and Bacteria.

  DOI：

  10.1016/j.chembiol.2014.07.022

文献信息

• Geranylgeranylglyceryl Phosphate Synthase. Characterization of the Recombinant Enzyme from <i>Methanobacterium thermoautotrophicum</i>
  作者：Tim Soderberg、Anjun Chen、C. Dale Poulter

  DOI：10.1021/bi0111799

  日期：2001.12.1

  was purified to homogeneity. The enzyme is active as a homopentamer, as determined by size exclusion chromatography and equilibrium sedimentation experiments. GGGP synthase has optimal activity at 55 degrees C in pH 8.0 buffer containing 1 mM MgCl(2). V(max) = 4.0 +/- 0.1 micromol min(-1) mg(-1) (k(cat) = 0.34 +/- 0.03 s(-1) for pentameric GGGP synthase assuming all subunits are fully active), K(m)((S)-GP)

  香叶基香叶基甘油基二磷酸甘油酯合酶（GGGP合酶）催化香叶基香叶基二磷酸甘油酯（GGPP）催化（S）-甘油基磷酸酯[（S）-GP]的烷基化反应，从而生成（S）-香叶基香叶基甘油基磷酸酯[[S] -GGGP]。该反应是古细菌中醚连接的膜脂质的生物合成中第一个重要的步骤。使用根据从纯化的酶确定的N-末端序列设计的探针，克隆来自嗜热自生甲烷菌的GGGP合酶的基因。将编码245个氨基酸的蛋白质的开放阅读框插入pET表达载体，并在大肠杆菌中表达。重组GGGP合酶被纯化至同质。通过尺寸排阻色谱法和平衡沉降实验确定，该酶具有作为均戊烯的活性。GGGP合酶在55摄氏度，含有1 mM MgCl（2）的pH 8.0缓冲液中具有最佳活性。V（max）= 4.0 +/- 0.1 micromol min（-1）mg（-1）（假设所有亚基均具有完全活性，五聚体GGGP合酶的k（cat）= 0.34 +/- 0.03
• Functional Assignment of an Enzyme that Catalyzes the Synthesis of an Archaea-Type Ether Lipid in Bacteria
  作者：Harald Guldan、Frank-Michael Matysik、Marco Bocola、Reinhard Sterner、Patrick Babinger

  DOI：10.1002/anie.201101832

  日期：2011.8.22

  An archaea‐type ether lipid in bacteria: PcrB, the bacterial homologue of the archaea‐specific geranylgeranylglyceryl phosphate synthase, produces heptaprenylglyceryl phosphate in bacillales. The product becomes dephosphorylated and acetylated in vivo.

  细菌中的古细菌型醚脂质：PcrB，即古细菌特有的香叶基香叶基甘油磷酸酯合酶的细菌同源物，可在杆菌中产生七戊基甘油基磷酸酯。该产物在体内被去磷酸化和乙酰化。
• Purification and Characterization of Geranylgeranylglyceryl Phosphate Synthase from a Thermoacidophilic Archaeon, Thermoplasma acidophilum
  作者：N. Nemoto

  DOI：10.1093/jb/mvg083

  日期：2003.5.1

  We purified a geranylgeranylglyceryl phosphate (GGGP) synthase from Thermoplasma acidophilum by several steps of chromatography. Based on the proteinase-fragment-mass-pattern analysis of the SDS-PAGE band of the partially purified protein, the DNA sequence encoding the protein was identified from the whole genome sequence database of the species. The gene encoding GGGP synthase in T. acidophilum was cloned after PCR amplification of the gene from the genomic DNA. The recombinant enzyme was expressed in Escherichia coli and purified. A single band with a molecular mass of 27 kDa was obtained by SDS-PAGE analysis. The apparent native molecular mass of the enzyme was about 50 kDa based on gel filtration chromatography, suggesting that the enzyme is active as a homodimer. As the GGGP synthase from Methanobacterium thermoautotrophicum has been reported as a pentamer, the enzymes of the two organisms have different oligomeric structures. Other characteristics, including substrate specificity, are similar for the GGGPs of these organisms.

  我们采用色谱法对嗜热酸杆菌中的甘油磷酸二烯丙基甘油酯（GGGP）合成酶进行了多步纯化。根据对部分纯化蛋白的SDS-PAGE条带进行的蛋白酶片段质量模式分析，从该物种的全基因组序列数据库中确定了编码该蛋白的DNA序列。在从基因组DNA中PCR扩增嗜热酸杆菌中GGGP合成酶的基因后，将其克隆。重组酶在大肠杆菌中表达并纯化。通过SDS-PAGE分析得到一条分子质量为27 kDa的条带。根据凝胶过滤色谱法，该酶的表观天然分子质量约为50 kDa，表明该酶作为同源二聚体是活跃的。由于来自热自养甲烷杆菌的GGGP合成酶已被报道为五聚体，因此这两种生物的酶具有不同的低聚结构。这些生物的GGGP的其他特征（包括底物特异性）是相似的。
• Specific Partial Reduction of Geranylgeranyl Diphosphate by an Enzyme from the Thermoacidophilic Archaeon <i>Sulfolobus acidocaldarius</i> Yields a Reactive Prenyl Donor, Not a Dead-End Product
  作者：Sho Sato、Motomichi Murakami、Tohru Yoshimura、Hisashi Hemmi

  DOI：10.1128/jb.00082-08

  日期：2008.6

  Geranylgeranyl reductase from Sulfolobus acidocaldarius was shown to catalyze the reduction of geranylgeranyl groups in the precursors of archaeal membrane lipids, generally reducing all four double bonds. However, when geranylgeranyl diphosphate was subjected to the reductase reaction, only three of the four double bonds were reduced. Mass spectrometry and acid hydrolysis indicated that the allylic double bond was preserved in the partially reduced product derived from geranylgeranyl diphosphate. Thus, the reaction product was shown to be phytyl diphosphate, which is a substrate for archaeal prenyltransferases, unlike the completely reduced compound phytanyl diphosphate.

  摘要 香叶基纯碱还原酶来自 中的香叶基还原酶 可催化古生膜脂质前体中的香叶基还原基团还原，一般可还原所有四个双键。然而，当对二磷酸香叶酯进行还原酶反应时，四个双键中只有三个被还原。质谱分析和酸水解表明，在二磷酸香叶酯的部分还原产物中保留了烯丙基双键。因此，与完全还原的二磷酸植丹酰化合物不同，反应产物被证明是二磷酸植丹酰，它是古细菌前酰转移酶的底物。
• CTP:2,3-di-O-geranylgeranyl-sn-glycero-1-phosphate Cytidyltransferase in the Methanogenic ArchaeonMethanothermobacter thermoautotrophicus
  作者：Hiroyuki Morii、Masateru Nishihara、Yosuke Koga

  DOI：10.1074/jbc.m005925200

  日期：2000.11

  CDP-S, 3-di-O-geranylgeranyl-sn-glycerol synthase (CDP-archaeol synthase) activity was discovered in the membrane fraction of the methanoarchaeon Methano-thennobacter thermoautotrophicus cells. It catalyzed the formation of CDP-2,3-di-O-geranylgeranyl-sn-glycerol from CTP and 2,3-di-O-geranylgeranyl-sn-glycero-1-phosphate (unsaturated archaetidic acid). The identity of the reaction product was confirmed by thin layer chromatography, fast atom bombardment-mass spectroscopy, chemical analysis, and by UV spectroscopy. One mole of the product was formed hom approximately 1 mol of each of the reactants. The enzyme showed maximal. activity at pH 8.5 and 55 degreesC in the presence of Mg2+ and K+ ions. By in vivo pulse labeling of phospholipids with P-32(i), CDP-archaeol was found to be an intracellular intermediate. A cell-free homogenate of Bf. thermoautotrophicus, when incubated with L-serine, converted the product of CDP-archaeol synthase reaction to a product with the same chromatographic mobility as archaetidylserine. It was concluded from these results that both CDP-archaeol and CDP-archaeol synthase were involved in cellular phospholipid biosynthesis. Among various synthetic substrate analogs, both enantiomers of unsaturated archaetidic acid possessing geranylgeranyl chains showed similar levels of activity, while archaetidic acid with saturated or monounsaturated isoprenoid or straight chains was a poor substrate, despite having the same stereostructure as the fully active substrate. The ester analogs with geranylgeranioyl chains showed significant activities. These results suggest that the enzyme dose not recognize ether or ester bonds between glycerophosphate and hydrocarbon chains nor the stereostructure of the glycerophosphate backbone but mainly targets substrates with geranylgeranyl chains.