C55 prenyl diphosphate

• 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: C55 prenyl diphosphate
• 英文别名: Di-trans,octa-cis-undecaprenyl diphosphate；[oxido-[(2Z,6Z,10Z,14Z,18Z,22Z,26Z,30Z,34E,38E)-3,7,11,15,19,23,27,31,35,39,43-undecamethyltetratetraconta-2,6,10,14,18,22,26,30,34,38,42-undecaenoxy]phosphoryl] phosphate
• 化学式: C₅₅H₈₉O₇P₂
• 分子量: 924.255
• InChiKey: NTXGVHCCXVHYCL-NTDVEAECSA-K

计算性质

• 辛醇/水分配系数(LogP)：
  17.2
• 重原子数：
  64
• 可旋转键数：
  34
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  122
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2R,4R,5R,6R)-2-[(2R,4R,5R,6R)-2-carboxylato-6-[(1R)-1,2-dihydroxyethyl]-2-[[(2R,3S,4R,5R,6R)-5-[[(3R)-3-dodecanoyloxy-1-oxidotetradecylidene]amino]-6-[[(2R,3S,4R,5R,6R)-3-hydroxy-5-[[(3R)-3-hydroxy-1-oxidotetradecylidene]amino]-4-[(3R)-3-hydroxytetradecanoyl]oxy-6-phosphonooxyoxan-2-yl]methoxy]-3-phosphonatooxy-4-[(3R)-3-tetradecanoyloxytetradecanoyl]oxyoxan-2-yl]methoxy]-5-hydroxyoxan-4-yl]oxy-6-[(1R)-1,2-dihydroxyethyl]-4,5-dihydroxyoxane-2-carboxylate 、 C55 prenyl diphosphate 生成 alpha-D-Kdo-(2->4)-alpha-D-Kdo-(2->6)-lipid A 1-diphosphate 、 di-trans,octa-cis-Undecaprenyl phosphate
  参考文献：
  名称：

  脂质 A 的周质磷酸化与十一碳烯磷酸酯的合成有关。

  摘要：

  在大肠杆菌外膜中发现的脂质 A 的三分之一在位置 1（脂质 A 1-二磷酸）含有未取代的二磷酸单元。我们现在报告了一种内膜酶 LpxT (YeiU)，它专门将磷酸基团转移到脂质 A，形成 1-二磷酸物种。(32) 从 lpxT 突变体中获得的 P 标记的脂质 A 不产生脂质 A 1-二磷酸。以 Kdo(2)-[4'-(32)P]lipid A 作为受体的体外测定表明 LpxT 使用十一碳烯焦磷酸作为底物供体。通过用环状多肽抗生素杆菌肽螯合十一碳烯焦磷酸酯，证明了对野生型细菌中脂质 A 1-二磷酸酯形成的抑制，提供了十一碳烯焦磷酸酯作为整个细菌内的供体底物的证据。LpxT 催化的磷酸化依赖于脂质 A 通过 MsbA（一种脂质 A 翻转酶）穿过内膜的转运，表明存在周质活性位点。总之，我们展示了脂质 A 周质修饰的新途径，该途径与磷酸十一碳烯酯的合成直接相关，磷酸十一碳烯酯是合成各种细菌聚合物（如肽聚糖）所需的必需载体脂质。

  DOI：

  10.1111/j.1365-2958.2007.06044.x
• 作为产物：
  描述：

  isopentenyl pyrophosphate 、 farnesyl pyrophosphate 在 ditrans,polycis-undecaprenyl-diphosphate synthase [(2E,6E)-farnesyl-diphosphate specific] 作用下， 生成 C55 prenyl diphosphate
  参考文献：
  名称：

  酶法合成甘氨醇

  摘要：

  大豆叶片中发现的新型戊烯醇甘露醇-9，-10和-11是通过十一碳烯基二磷酸合酶的作用通过植酸基和异戊烯基二磷酸合成，然后进行酸性磷酸酶处理而合成的。

  DOI：

  10.1016/0040-4039(91)80865-4

文献信息

• A conserved C-terminal RXG motif in the NgBR subunit of cis-prenyltransferase is critical for prenyltransferase activity
  作者：Kariona A. Grabińska、Ban H. Edani、Eon Joo Park、Jan R. Kraehling、William C. Sessa

  DOI：10.1074/jbc.m117.806034

  日期：2017.10

  cis-Prenyltransferases (cis-PTs) constitute a large family of enzymes conserved during evolution and present in all domains of life. In eukaryotes and archaea, cis-PT is the first enzyme committed to the synthesis of dolichyl phosphate, an obligate lipid carrier in protein glycosylation reactions. The homodimeric bacterial enzyme, undecaprenyl diphosphate synthase, generates 11 isoprene units and has

  顺式-苯甲酰转移酶（cis-PTs）构成了进化过程中保守并存在于生活所有领域的一大类酶。在真核生物和古细菌中，顺式-PT是致力于合成磷酸二氢磷酸酯的第一种酶，磷酸二氢磷酸酯是蛋白质糖基化反应中的专性脂质载体。同型二聚体细菌酶十一碳烯基二磷酸合酶可产生11个异戊二烯单元，并已在结构和机械上进行了详细的表征。最近，我们发现，与十一碳二烯基二磷酸合酶不同，哺乳动物的顺式-PT是由NgBR（Nus1）和hCIT（脱氢二羟乙醇二磷酸合酶）亚基组成的杂聚体，这种成分已在植物和真菌的顺式-PT中得到证实。这里，我们建立了第一个用于异源顺式PT的纯化系统，并显示NgBR和hCIT亚基均在催化和底物结合中起作用。最后，我们在NgBR的C末端尾部确定了一个关键的RXG序列，该序列是保守的，对于跨门的酶活性至关重要。总之，我们的发现表明，真核生物顺式-PT由NgBR和hCIT亚基组成。NgBR直系同源物中RXG
• Crystal structure of <i>cis</i> -prenyl chain elongating enzyme, undecaprenyl diphosphate synthase
  作者：Masahiro Fujihashi、Yuan-Wei Zhang、Yoshiki Higuchi、Xiao-Yuan Li、Tanetoshi Koyama、Kunio Miki

  DOI：10.1073/pnas.071514398

  日期：2001.4.10

  Undecaprenyl diphosphate synthase (UPS) catalyzes the cis -prenyl chain elongation onto trans , trans -farnesyl diphosphate (FPP) to produce undecaprenyl diphosphate (UPP), which is indispensable for the biosynthesis of bacterial cell walls. We report here the crystal structure of UPS as the only three-dimensional structure among cis -prenyl chain elongating enzymes. The structure is classified into a protein fold family and is completely different from the so-called “isoprenoid synthase fold” that is believed to be a common structure for the enzymes relating to isoprenoid biosynthesis. Conserved amino acid residues among cis -prenyl chain elongating enzymes are located around a large hydrophobic cleft in the UPS structure. A structural P-loop motif, which frequently appears in the various kinds of phosphate binding site, is found at the entrance of this cleft. The catalytic site is determined on the basis of these structural features, from which a possible reaction mechanism is proposed.

  Undecaprenyl二磷酸合酶(UPS)催化将cis-预醇链延长到trans, trans-法尼醇二磷酸(FPP)上，产生不十一烷二磷酸(UPP)，这对于细菌细胞壁的生物合成是必不可少的。我们在此报告UPS的晶体结构，它是唯一的三维结构，属于蛋白质折叠家族，并且与所谓的“异戊烯合成酶折叠”完全不同，后者被认为是与异戊烯生物合成有关的酶的共同结构。在UPS结构中，保守的氨基酸残基位于一个大的疏水裂隙周围，这些氨基酸残基是cis-预醇链延伸酶中的共同点。在该裂隙的入口处发现了一个结构P环基序，它经常出现在各种磷酸盐结合位点中。基于这些结构特征，确定了催化位点，并提出了可能的反应机制。
• Undecaprenyl pyrophosphate synthetase from Lactobacillus plantarum: A dimeric protein
  作者：J.D. Muth、Charles M. Allen

  DOI：10.1016/0003-9861(84)90085-7

  日期：1984.4

  a++Undecaprenyl pyrophosphate synthetase has been purified from Lactobacillus plantarum. It catalyzes the formation of a C55 polyprenyl pyrophosphate having isoprene residues with cis stereochemistry. The enzyme was shown to be an acidic protein (pI = 5.1), which can be partially purified by preparative gel electrophoresis and Blue-agarose column chromatography. The Km's of the enzyme for its substrates

  已经从植物乳杆菌中纯化了α++十一碳烯基焦磷酸合成酶。它通过顺式立体化学催化形成具有异戊二烯残基的C55聚异戊二烯基焦磷酸盐。该酶显示为酸性蛋白（pI = 5.1），可以通过制备性凝胶电泳和Blue-agarose柱色谱法进行部分纯化。测定其底物t，t-法呢基焦磷酸和异戊烯基焦磷酸的酶的Km分别为0.13和1.92microM。通过分子筛色谱法和梯度离心法估计该酶的分子量为56,000 +/- 4000。通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳的分析表明该蛋白质由30,000Da亚基的二聚体组成。
• The bacA Gene of Escherichia coli Encodes an Undecaprenyl Pyrophosphate Phosphatase Activity
  作者：Meriem El Ghachi、Ahmed Bouhss、Didier Blanot、Dominique Mengin-Lecreulx

  DOI：10.1074/jbc.m401701200

  日期：2004.7

  The bacA gene, the overexpression of which results in bacitracin resistance, was inactivated and shown to be non-essential for growth of Escherichia coli. It was proposed earlier that the bacA gene product may confer resistance to the antibiotic by phosphorylation of undecaprenol (Cain, B. D., Norton, P. J., Eubanks, W., Nick, H. S., and Allen, C. M. (1983) J. Bacteriol. 175, 3784-3789). In the present work, this extremely hydrophobic membrane protein was overproduced and purified to near homogeneity. The analysis of its catalytic properties clearly demonstrated that the purified BacA protein exhibited undecaprenyl pyrophosphate phosphatase activity but not undecaprenol phosphokinase activity. This finding was perfectly consistent with the mechanism of action of bacitracin that consists in the sequestration of undecaprenyl pyrophosphate, the BacA enzyme substrate. The level of undecaprenyl pyrophosphate phosphatase was increased by 280-fold in cells carrying bacA on a multicopy expression plasmid. It was decreased by similar to75% but was not completely abolished in a bacA disruption mutant, suggesting that BacA is the main E. coli undecaprenyl pyrophosphate phosphatase but that other protein(s) exhibiting such an activity should exist to account for the residual activity and viability of the mutant strain. This is the first gene encoding undecaprenyl pyrophosphate phosphatase identified to date. Considering its newly identified function, we propose to rename the bacA gene uppP.
• Mechanism of Product Chain Length Determination and the Role of a Flexible Loop in Escherichia coliUndecaprenyl-pyrophosphate Synthase Catalysis
  作者：Tzu-Ping Ko、Yi-Kai Chen、Howard Robinson、Pei-Chun Tsai、Yi-Gui Gao、Annie P.-C. Chen、Andrew H.-J. Wang、Po-Huang Liang

  DOI：10.1074/jbc.m106747200

  日期：2001.12

  The Escherichia coli undecaprayl-pyrophosphate synthase (UPPs) structure has been solved using the single wavelength anomalous diffraction method. The putative substrate-binding site is located near the end of the betaA-strand with Asp-26 playing a critical catalytic role. In both subunits, an elongated hydrophobic tunnel is found, surrounded by four beta -strands (betaA-betaB-betaD-betaC) and two helices (alpha2 and alpha3) and lined at the bottom with large residues Ile-62, Leu-137, Val-105, and His-103. The product distributions formed by the use of the I62A, V105A, and H103A mutants are similar to those observed for wild-type UPPs. Catalysis by the L137A UPPs, on the other hand, results in predominantly the formation of the C-70 polymer rather than the C-55 polymer. Ala-69 and Ala-143 are located near the top of the tunnel. In contrast to the A143V reaction, the C-30 intermediate is formed to a greater extent and is longer lived in the process catalyzed by the A69L mutant. These findings suggest that the small side chain of Ala-69 is required for rapid elongation to the C-55 product, whereas the large hydrophobic side chain of Leu-137 is required to limit the elongation to the C-55 product. The roles of residues located on a flexible loop were investigated. The S71A, N74A, or R77A mutants displayed 25-200-fold decrease in k(cat) values. W75A showed an 8-fold increase of the FPP K-m value, and 22-33-fold increases in the IPP K-m values were observed for E81A and S71A. The loop may function to bridge the interaction of IPP with FPP, needed to initiate the condensation reaction and serve as a hinge to control the substrate binding and product release.