guanosine 5'-diphospho-β-L-fucose | 160956-08-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 英文名称: guanosine 5'-diphospho-β-L-fucose
• 英文别名: guanosine 5'-(β-L-fucopyranosyl)-diphosphate；GDP-fucose；GDP-beta-L-fucose(2-)；[[(2R,3S,4R,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl] [(2R,3S,4R,5S,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl] phosphate
• CAS: 160956-08-1
• 化学式: C₁₆H₂₃N₅O₁₅P₂
• 分子量: 587.331
• InChiKey: LQEBEXMHBLQMDB-JGQUBWHWSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  -6.7
• 重原子数：
  38
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  313
• 氢给体数：
  7
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  guanosine 5'-diphospho-β-L-fucose 、 在 human milk α-(1->3/4)-fucosyltransferase (3/4-Fuc-T) 作用下， 反应 24.0h， 生成 O-(sodium 5-acetamido-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulpyranosyluronate)-(2->3)-O-β-D-galactopyranosyl-(1->3)-O-[α-L-fucopyranosyl-(1->4)]-O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-(1->3)-O-β-D-galactopyranosyl-(1->4)-D-[N-acetyl-N-...]...
  参考文献：
  名称：

  还原性低聚糖的新衍生物及其在酶促反应中的应用：唾液酸化的Lewis a和唾液酸二聚的Lewis x糖缀合物的有效合成

  摘要：

  用苄氧基羰基氨基苯胺和氰基硼氢化钠将还原性低聚糖乳糖和乳糖-N-四糖还原胺化，然后用乙酸酐处理所得仲胺。用各种糖基转移酶/核苷酸糖对所得的N-乙酰基-N-（4-苄氧基羰基氨基苯基）-1-氨基-1-脱氧醛二糖寡糖衍生物进行逐步酶促延伸。通过在硅胶C-18柱上进行固相萃取，可以方便地进行每个酶促步骤后产物的纯化。制备了两种寡糖衍生物（具有唾液酸化的路易斯a和唾液酸化的二聚Lewis x结构）。通过顺序氢解，硫光气处理和蛋白质偶联，将获得的衍生物转化为新糖蛋白。

  DOI：

  10.1016/s0008-6215(00)00128-2
• 作为产物：
  描述：

  GMP-morpholidate 、 bis(triethylammonium) β-L-fucopyranosyl 1-phosphate 在 吡啶 作用下， 反应 5.0h， 生成 guanosine 5'-diphospho-β-L-fucose
  参考文献：
  名称：

  Efficient chemical synthesis of GDP-fucose

  摘要：

  DOI：

  10.1021/jo00036a036

文献信息

• Cloning and Characterization of the α(1,3/4) Fucosyltransferase of Helicobacter pylori
  作者：David A. Rasko、Ge Wang、Monica M. Palcic、Diane E. Taylor

  DOI：10.1074/jbc.275.7.4988

  日期：2000.2

  to add fucose with a greater than 5-fold preference for type II chains but still retains significant activity using type I acceptors. The addition of the fucose to the type II carbohydrate acceptors, by UA948FucTa, does not appear to be affected by fucosylation at other sites on the carbohydrate acceptor, but the rate of fucose transfer is affected by terminal fucosylation of type I acceptors. Through

  胃病原体幽门螺杆菌可以表达许多人类细胞表面的组织血型抗原。大多数幽门螺杆菌菌株表达II型碳水化合物，路易斯X和Y，而少数人群表达I型碳水化合物，路易斯A和B。路易斯A和路易斯X的表达，如幽门螺杆菌UA948一样。 ，要求分别在I，II型碳水化合物主链的alpha1,4和alpha1,3连接中添加岩藻糖。这项工作描述了单个幽门螺杆菌岩藻糖基转移酶（FucT）的克隆和鉴定，该酶具有将岩藻糖以类似于人岩藻糖基转移酶V（Fuc-TV）的方式转移至上述两个连接的能力。已经在每个测序的基因组中鉴定出两个fucT基因的同源拷贝。编码两个UA948fucT基因的DNA中存在氨基末端和羧基末端重复区域中的特征性腺苷和胞嘧啶区，但与先前鉴定的幽门螺杆菌fucTs相比，这些基因也包含差异。UA948fucTa基因编码包含475个氨基酸的约52kDa蛋白，而UA948fucTb不编码全长FucT蛋白。在体外，UA
• Distantly related plant and nematode core α1,3-fucosyltransferases display similar trends in structure–function relationships
  作者：Peter Both、Lukas Sobczak、Christelle Breton、Stephan Hann、Katharina Nöbauer、Katharina Paschinger、Stanislav Kozmon、Ján Mucha、Iain B H Wilson

  DOI：10.1093/glycob/cwr056

  日期：2011.11

  Here, we present a comparative structure–function study of a nematode and a plant core α1,3-fucosyltransferase based on deletion and point mutations of the coding regions of Caenorhabditis elegans FUT-1 and Arabidopsis thaliana FucTA (FUT11). In particular, our results reveal a novel “first cluster motif” shared by both core and Lewis-type α1,3-fucosyltransferases of the GT10 family. To evaluate the role of the conserved serine within this motif, this residue was replaced with alanine in FucTA (S218) and FUT-1 (S243). The S218A replacement completely abolished the enzyme activity of FucTA, while the S243A mutant of FUT-1 retained 20% of the “wild-type” activity. Based on the results of homology modeling of FucTA, other residues potentially involved in the donor substrate binding were examined, and mutations of N219 and R226 dramatically affected enzymatic activity. Finally, as both FucTA and FUT-1 were shown to be N-glycosylated, we examined the putative N-glycosylation sites. While alanine replacements at single potential N-glycosylation sites of FucTA resulted in a loss of up to 80% of the activity, a triple glycosylation site mutant still retained 5%, as compared to the control. In summary, our data indicate similar trends in structure–function relationships of distantly related enzymes which perform similar biochemical reactions and form the basis for future work aimed at understanding the structure of α1,3-fucosyltransferases in general.

  在此，我们基于秀丽隐杆线虫FUT-1和拟南芥FucTA（FUT11）编码区域的缺失和点突变，对线虫和植物核心α1,3-岩藻糖基转移酶进行了结构-功能比较研究。 特别是，我们的研究结果揭示了GT10家族的核心和Lewis型α1,3-岩藻糖基转移酶共享的新颖“第一簇基序”。 为了评估该基序中保守丝氨酸的作用，在FucTA（S218）和FUT-1（S243）中用丙氨酸替换了该残基。 S218A替换完全消除了FucTA的酶活性，而FUT-1的S243A突变体保留了20%的“野生型”活性。 根据FucTA的同源建模结果，我们检查了可能参与供体底物结合的其他残基，发现N219和R226的突变会显著影响酶活性。 最后，由于FucTA和FUT-1都被证明是N-糖基化的，我们检查了推测的N-糖基化位点。 虽然FucTA单个潜在N-糖基化位点的丙氨酸替换导致活性丧失高达80%，但与对照组相比，三糖基化位点突变体仍保留了5%的活性。 总之
• Molecular cloning and characterization of an  1,3 fucosyltransferase, CEFT-1, from Caenorhabditis elegans
  作者：R. A. DeBose-Boyd、A. K. Nyame、R. D. Cummings

  DOI：10.1093/glycob/8.9.905

  日期：1998.9.1

  We report on the identification, molecular cloning, and characterization of an α1,3 fucosyltransferase (α1,3FT) expressed by the nematode, Caenorhabditis elegans. Although C.elegans glycoconjugates do not express the Lewis x antigen Galβ1→4[Fucα1→3]GlcNAcβ→R, detergent extracts of adult C.elegans contain an α1,3FT that can fucosylate both nonsialylated and sialylated acceptor glycans to generate the Lex and sialyl Lex antigens, as well as the lacdiNAc-containing acceptor GalNAcβ1→4GlcNAcβ1→R to generate GalNAcβ1→4 [Fucα1→3]GlcNAcβ1→R. A search of the C.elegans genome database revealed the existence of a gene with 20–23% overall identity to all five cloned human α1,3FTs. The putative cDNA for the C.elegans α1,3FT (CEFT-1) was amplified by PCR from a cDNA λZAP library, cloned, and sequenced. COS7 cells transiently transfected with cDNA encoding CEFT-1 express the Lex, but not sLex antigen. The CEFT-1 in the transfected cell extracts can synthesize Lex, but not sialyl Lex, using exogenous acceptors. A second fucosyltransferase activity was detected in extracts of C.elegans that transfers Fuc in α1,2 linkage to Gal specifically on type-1 chains. The discovery of α-fucosyltransferases in C.elegans opens the possibility of using this well-characterized nematode as a model system for studying the role of fucosylated glycans in the development and survival of C.elegans and possibly other helminths.

  我们报告了线虫秀丽隐杆线虫表达的α1,3岩藻糖基转移酶（α1,3FT）的鉴定、分子克隆和特征描述。虽然秀丽隐杆线虫的聚糖不表达 Lewis x 抗原 Galβ1→4[Fucα1→3]GlcNAcβ→R，但成年秀丽隐杆线虫的洗涤剂提取物中含有α1,3FT。秀丽隐杆线虫含有一种 α1,3FT，它能对非硅烷基化和硅烷基化的受体聚糖进行岩藻糖基化，生成 Lex 和硅烷基 Lex 抗原，还能对含 lacdiNAc 的受体 GalNAcβ1→4GlcNAcβ1→R 进行岩藻糖基化，生成 GalNAcβ1→4[Fucα1→3]GlcNAcβ1→R 。通过对 elegans 基因组数据库的搜索，发现了一个与所有五个克隆的人类 α1,3FTs具有 20-23% 相同度的基因。通过 PCR 从 cDNA λZAP 文库中扩增出了 elegans α1,3FT（CEFT-1）的推定 cDNA，并对其进行了克隆和测序。瞬时转染了编码 CEFT-1 的 cDNA 的 COS7 细胞能表达 Lex 抗原，但不能表达 sLex 抗原。转染细胞提取物中的 CEFT-1 能利用外源受体合成 Lex，但不能合成 sialyl Lex。在秀丽隐杆线虫的提取物中检测到了第二种岩藻糖基转移酶活性，它能将α1,2连接的岩藻糖转移到1型链上的Gal上。在秀丽隐杆线虫中发现α-岩藻糖基转移酶为研究岩藻糖基化聚糖在秀丽隐杆线虫以及其他蠕虫的发育和生存过程中的作用提供了可能。
• In vitro bacterial polysaccharide biosynthesis: defining the functions of Wzy and Wzz
  作者：Robert Woodward、Wen Yi、Lei Li、Guohui Zhao、Hironobu Eguchi、Perali Ramu Sridhar、Hongjie Guo、Jing Katherine Song、Edwin Motari、Li Cai、Patrick Kelleher、Xianwei Liu、Weiqing Han、Wenpeng Zhang、Yan Ding、Mei Li、Peng George Wang

  DOI：10.1038/nchembio.351

  日期：2010.6

  O-polysaccharide is a major constituent of the bacterial cell wall, yet little mechanistic information is known about its biosynthesis. A reconstruction of this pathway using defined substrates now demonstrates the basis for sugar polymerization and length modulation. Polysaccharides constitute a major component of bacterial cell surfaces and play critical roles in bacteria–host interactions. The biosynthesis of such molecules, however, has mainly been characterized through in vivo genetic studies, thus precluding discernment of the details of this pathway. Accordingly, we present a chemical approach that enabled reconstitution of the E. coli O-polysaccharide biosynthetic pathway in vitro. Starting with chemically prepared undecaprenyl-diphospho-N-acetyl-D-galactosamine, the E. coli O86 oligosaccharide repeating unit was assembled by means of sequential enzymatic glycosylation. Successful expression of the putative polymerase Wzy using a chaperone coexpression system then allowed demonstration of polymerization in vitro using this substrate. Analysis of more substrates revealed a defined mode of recognition for Wzy toward the lipid moiety. Specific polysaccharide chain length modality was furthermore demonstrated to result from the action of Wzz. Collectively, polysaccharide biosynthesis was chemically reconstituted in vitro, providing a well defined system for further underpinning molecular details of this biosynthetic pathway.

  O 型多糖是细菌细胞壁的主要成分，但人们对其生物合成的机理知之甚少。现在，利用确定的底物重建这一途径证明了糖聚合和长度调节的基础。 多糖是细菌细胞表面的主要成分，在菌鬼相互作用中起着关键作用。然而，这类分子的生物合成主要是通过体内基因研究来确定的，因此无法确定这一途径的细节。因此，我们提出了一种能在体外重建大肠杆菌 O 型多糖生物合成途径的化学方法。从化学制备的十一烯丙基-二磷酸-N-乙酰-D-半乳糖胺开始，大肠杆菌 O86 寡糖重复单元通过连续的酶糖基化组装而成。然后，利用伴侣共表达系统成功表达了推定聚合酶 Wzy，从而在体外证明了这种底物的聚合作用。对更多底物的分析表明，Wzy 对脂质分子有明确的识别模式。Wzz 的作用还进一步证明了特定的多糖链长度模式。总之，多糖的生物合成是在体外通过化学方法重建的，这为进一步证实这一生物合成途径的分子细节提供了一个定义明确的系统。
• Stereochemical Course and Steady State Mechanism of the Reaction Catalyzed by the GDP-fucose Synthetase from Escherichia coli
  作者：Saurabh Menon、Mark Stahl、Ravindra Kumar、Guang-Yi Xu、Francis Sullivan

  DOI：10.1074/jbc.274.38.26743

  日期：1999.9

  that it catalyzes epimerizations and a reduction reaction at the same active site. This aspect separates fucose biosynthesis from that of other deoxy and dideoxy sugars in which the epimerase and reductase activities are present on separate enzymes encoded by separate genes. By NMR spectroscopy we have shown that GFS catalyzes the stereospecific hydride transfer of the ProS hydrogen from NADPH to carbon

  最近，已克隆了编码人和大肠杆菌GDP-甘露糖脱水酶和GDP-岩藻糖合成酶（GFS）蛋白的基因，并且已证明仅这两个蛋白就足以在体外将GDP甘露糖转化为GDP岩藻糖。来自大肠杆菌的GDP-岩藻糖合成酶是一种新型的双功能酶，因为它可以在同一活性位点催化差向异构和还原反应。这个方面将岩藻糖的生物合成与其他脱氧和双脱氧糖的合成分开，在这些其他的脱氧和双脱氧糖中，差向异构酶和还原酶活性存在于由独立基因编码的独立酶上。通过NMR光谱，我们已经表明GFS催化了ProS氢从NADPH到甘露糖的碳4的立体定向氢化物转移。这与对于GFS为成员的短链脱氢酶还原酶家族的其他成员所观察到的立体特异性一致。另外，在不存在NADP或NADPH的情况下，该酶能够催化差向异构反应。通过产物抑制和荧光结合研究确定的GFS的动力学机制与随机机制一致。从荧光研究确定的解离常数表明，与产物NADP相比，该酶对底物NADPH的亲和力强