2,3-bis-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: 2,3-bis-O-geranylgeranyl sn-glycerol-1-phosphate
• 英文别名: DGGGP；2,3-bis-O-(geranylgeranyl)-sn-glycerol 1-phosphate(2-)；[(2S)-2,3-bis[(2E,6E,10E)-3,7,11,15-tetramethylhexadeca-2,6,10,14-tetraenoxy]propyl] phosphate
• 化学式: C₄₃H₇₁O₆P
• 分子量: 715.007
• InChiKey: WHMXLRRVANEOOG-MVFIEKMPSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  12.2
• 重原子数：
  50
• 可旋转键数：
  27
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  90.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,3-bis-O-geranylgeranyl sn-glycerol-1-phosphate 、 cytidine 5'-triphosphate 、 氢(+1)阳离子 生成 1-CDP-2,3-bis-O-geranylgeranyl sn-glycerol 、 pyrophosphoric acid
  参考文献：
  名称：

  CDP-2,3-Di -O- Geranylgeranyl- sn -Glycerol: l -Serine O -Archaetidyltransferase (Archaetidylserine Synthase) in the Methanogenic Archaeon Methanothermobacter thermautotrophicus

  摘要：

  摘要 CDP-2,3-二 -O- 香叶基 甘油 -甘油： l -丝氨酸 O -的细胞提取物中的古乙酰转移酶（古乙酰丝氨酸合成酶）活性。 的活性进行了表征。 的活性进行了表征。该酶催化 CDP-不饱和古醇和 lDP-不饱和古丝氨酸的形成。 l -丝氨酸。反应产物的特征通过薄层色谱法、快速原子轰击质谱分析和化学降解得到了证实。该酶在 10 mM Mn 2+ 和 1% Triton X-100 的条件下，酶的活性达到最高。在各种合成底物类似物中，具有醚键香叶基纯正甘油链的 CDP 不饱和古醇和具有醚键植烷酰链的 CDP 饱和古醇的两种对映体对古乙酰丝氨酸合成酶具有类似的活性。对底物的酯类似物的活性比对相应的醚型底物的活性高 2 到 3 倍。对 d -丝氨酸合成酶活性的 30%。 l -的 30%。通过脉冲标记实验，在细胞中检测到了微量的酸性不饱和古乙酰丝氨酸中间体。热自养菌中的一个基因（MT1027） 基因组中的一个基因（MT1027 基因组中被注释为编码磷脂酰丝氨酸合成酶的基因（MT1027）与 枯草芽孢杆菌 pssA 同源，但与 大肠杆菌 pssA 同源。 枯草芽孢杆菌磷脂酰丝氨酸合成酶的底物特异性 底物特异性 的底物特异性十分相似。 M. thermautotrophicus 的底物特异性十分相似，而大肠杆菌的 大肠杆菌 酶对 CDP-1,2-二乙酰基-丝氨酸有强烈的偏好。 甘油 -甘油。结论是 热自养蝠 古乙酰丝氨酸合成酶属于亚类 II 磷脂酰丝氨酸合成酶（B. subclass II phosphatidylserine synthase）。 B. subtilis 型），其依据不仅是同源性，还有底物特异性和一些酶学特性。本文讨论了编码亚类 II 磷脂酰丝氨酸合成酶的基因从细菌转移到甲烷菌祖先的可能性。

  DOI：

  10.1128/jb.185.4.1181-1189.2003
• 作为产物：
  描述：

  isopentenyl pyrophosphate 在 2,3-bis-O-geranylgeranyl sn-glycerol-1-phosphate synthase 、 3-O-geranylgeranyl sn-glycerol-1-phosphate synthase 、 magnesium 、 geranylgeranyl diphosphate synthase 作用下， 反应 1.0h， 生成 2,3-bis-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

• (S)-2,3-Di-O-geranylgeranylglyceryl Phosphate Synthase from the Thermoacidophilic Archaeon Sulfolobus solfataricus
  作者：Hisashi Hemmi、Kyohei Shibuya、Yoshihiro Takahashi、Toru Nakayama、Tokuzo Nishino

  DOI：10.1074/jbc.m409207200

  日期：2004.11

  in almost all archaeal genomes clearly indicates the importance of their functions. A phylogenetic tree constructed using the amino acid sequences of some typical members of the UbiA prenyltransferase family and their homologues from suggests that the two other homologues, excluding the ()-2,3-di--geranylgeranylglyceryl phosphate synthase, are involved in the production of respiratory quinone and heme

  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
• Biosynthesis of Archaeal Membrane Lipids: Digeranylgeranylglycerophospholipid Reductase of the Thermoacidophilic Archaeon Thermoplasma acidophilum
  作者：Yuji Nishimura、Tadashi Eguchi

  DOI：10.1093/jb/mvj118

  日期：2006.6.1

  The basic core structure of archaeal membrane lipids is 2,3-di-O-phytanyl-sn-glyceryl phosphate (archaetidic acid), which is formed by the reduction of 2,3-di-O-geranylgeranylglyceryl phosphate. The reductase activity for the key enzyme in membrane lipid biosynthesis, 2,3-digeranylgeranylglycerophospholipid reductase, was detected in a cell free extract of the thermoacidophilic archaeon Thermoplasma acidophilum. The reduction activity was found in the membrane fraction, and FAD and NADH were required for the activity. The reductase was purified from a cell free extract by ultracentrifugation and four chromatographic steps. The purified enzyme showed a single band at ca. 45 kDa on SDS-PAGE, and catalyzed the formation of archaetidic acid from 2,3-di-O-geranylgeranylglyceryl phosphate. Furthermore, the enzyme also catalyzed the reduction of 2,3-di-O-geranylgeranylglyceryl phosphate analogues such as 2,3-di-O-phytyl-sn-glyceryl phosphate, 3-O-(2,3-di-O-phytyl-sn-glycero-phospho)-sn-glycerol and 2,3-di-O-phytyl-sn-glycero-phosphoethanolamine. The N-terminal 20 amino acid sequence of the purified enzyme was determined and was found to be identical to the sequence encoded by the Ta0516m gene of the T. acidophilum genome. The present study clearly demonstrates that 2,3-digeranylgeranylglycerophospholipid reductase is a membrane associated protein and that the hydrogenation of each double bond of 2,3-digeranylgeranylglycerophospholipids is catalyzed by a single enzyme.

  古细菌膜脂质的基本核心结构是2,3-二-O-植物烷基-sn-甘油磷酸（古细菌酸），它是通过2,3-二-O-香叶基甘油磷酸的还原形成的。在嗜热古细菌嗜热古细菌的细胞外提取物中检测到了膜脂生物合成中的关键酶2,3-二-O-香叶基甘油磷酸还原酶的还原酶活性。还原活性存在于膜部分，并且需要FAD和NADH才能发挥作用。通过超速离心和四个色谱步骤从细胞外提取物中纯化了还原酶。纯化的酶在SDS-PAGE上显示约45 kDa的单条带，并催化了2,3-二-O-香叶基甘油磷酸形成古细菌酸。此外，该酶还催化了2,3-二-O-香叶基甘油磷酸类似物的还原，如2,3-二-O-植物烷基-sn-甘油磷酸、3-O-(2,3-二-O-植物烷基-sn-甘油磷酸)-sn-甘油醇和2,3-二-O-植物烷基-sn-甘油磷酸乙醇胺。确定了纯化酶的N端20个氨基酸序列，发现它与嗜热古细菌基因组中的Ta0516m基因编码的序列相同。本研究清楚地
• Insights into Substrate Specificity of Geranylgeranyl Reductases Revealed by the Structure of Digeranylgeranylglycerophospholipid Reductase, an Essential Enzyme in the Biosynthesis of Archaeal Membrane Lipids
  作者：Qingping Xu、Tadashi Eguchi、Irimpan I. Mathews、Christopher L. Rife、Hsiu-Ju Chiu、Carol L. Farr、Julie Feuerhelm、Lukasz Jaroszewski、Heath E. Klock、Mark W. Knuth、Mitchell D. Miller、Dana Weekes、Marc-André Elsliger、Ashley M. Deacon、Adam Godzik、Scott A. Lesley、Ian A. Wilson

  DOI：10.1016/j.jmb.2010.09.032

  日期：2010.12

  ligand-binding domain. Electron density corresponding to a bacterial lipid was found within this cavity. The cavity consists of a large opening that tapers down to two, narrow, curved tunnels that closely mimic the shape of the preferred substrate. We identified a sequence motif, PxxYxWxFP, that defines a specificity pocket in the enzyme and precisely aligns the double bond of the geranyl group with respect

  古菌膜脂由支链饱和烃组成，不同于细菌和真核生物中的那些。Digeranylgeranylglycerophospholipid还原酶（DGGR）催化氢化方法，其将不饱和的2,3-二- ø -geranylgeranylglyceryl磷酸盐至饱和2,3-二- ö-phytanylglyceryl phosphate 作为古菌膜脂生物合成的关键步骤。烃链的饱和度赋予了抗水解和氧化的能力，并有助于古细菌抵御极端条件。DGGR 是香叶基香叶基还原酶家族的成员，该家族也广泛分布于细菌和植物中，该家族成员参与光合色素的生物合成。我们已经确定了来自嗜热异养古菌嗜酸嗜热原菌的 DGGR 的晶体结构，分辨率为 1.6 Å，与黄素腺嘌呤二核苷酸 (FAD) 和细菌脂质复合。DGGR 结构可以分配给经过充分研究的p-羟基苯甲酸羟化酶 (PHBH) SCOP 黄素蛋白超家族，包括许多芳香族羟化酶和其他具有多种功能的酶。在
• 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.