uridine-5'-diphosphoglucose | 952585-00-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 英文名称: uridine-5'-diphosphoglucose
• 英文别名: UDP-glucose；UDP-Glc；uridine diphosphate glucose；uridine 5'-diphosphate-glucose；UDP-D-glucose；Uridin-5'-diphosphat-glucose；Uridindiphosphat-glucose；[[(2R,3S,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] hydrogen phosphate
• CAS: 952585-00-1
• 化学式: C₁₅H₂₄N₂O₁₇P₂
• 分子量: 566.306
• InChiKey: HSCJRCZFDFQWRP-RDKQLNKOSA-N

物化性质

• 密度：
  1.97±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -6.3
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  292
• 氢给体数：
  9
• 氢受体数：
  17

反应信息

• 作为反应物：
  描述：

  uridine-5'-diphosphoglucose 在 L-1,4-二硫代苏糖醇 、 Leishmania major UDP-sugar pyrophosphorylase 、 magnesium chloride 作用下， 生成 glucose 1-phosphate
  参考文献：
  名称：

  Leishmania UDP-sugar Pyrophosphorylase

  摘要：

  The Leishmania parasite glycocalyx is rich in galactose-containing glycoconjugates that are synthesized by specific glycosyltransferases that use UDP-galactose as a glycosyl donor. UDP-galactose biosynthesis is thought to be predominantly a de novo process involving epimerization of the abundant nucleotide sugar UDP-glucose by the UDP-glucose 4-epimerase, although galactose salvage from the environment has been demonstrated for Leishmania major. Here, we present the characterization of an L. major UDP-sugar pyrophosphorylase able to reversibly activate galactose 1-phosphate into UDP-galactose thus proving the existence of the Isselbacher salvage pathway in this parasite. The ordered bisubstrate mechanism and high affinity of the enzyme for UTP seem to favor the synthesis of nucleotide sugar rather than their pyrophosphorolysis. Although L. major UDP-sugar pyrophosphorylase preferentially activates galactose 1-phosphate and glucose 1-phosphate, the enzyme is able to act on a variety of hexose 1-phosphates as well as pentose 1-phosphates but not hexosamine 1-phosphates and hence presents a broad in vitro specificity. The newly identified enzyme exhibits a low but significant homology with UDP-glucose pyrophosphorylases and conserved in particular is the pyrophosphorylase consensus sequence and residues involved in nucleotide and phosphate binding. Saturation transfer difference NMR spectroscopy experiments confirm the importance of these moieties for substrate binding. The described leishmanial enzyme is closely related to plant UDP-sugar pyrophosphorylases and presents a similar substrate specificity suggesting their common origin.

  DOI：

  10.1074/jbc.m109.067223
• 作为产物：
  描述：

  尿苷-5'-三磷酸 在 UDPG pyrophosphorylase 作用下， 以 水 为溶剂， 反应 4.0h， 生成 uridine-5'-diphosphoglucose
  参考文献：
  名称：

  Yoza, Norimasa; Hirano, Hisanobu; Baba, Yoshinobu, Phosphorus and Sulfur and the Related Elements, 1987, vol. 30, p. 605 - 610

  摘要：

  DOI：
• 作为试剂：
  描述：

  尿苷-5'-三磷酸 、 D-吡喃葡萄糖 在 2(1H)-喹啉酮,1-丙基- 、 pyruvate kinase 、 无机焦磷酸酶 、 磷烯醇丙酮酸 、 galactose-1-phosphate uridylyltransferase 、 GalU 、 5’-三磷酸腺苷 、 uridine-5'-diphosphoglucose 作用下， 反应 24.0h， 以78%的产率得到UDP-Gal
  参考文献：
  名称：

  肺炎克雷伯菌UDP-d-吡喃半乳糖变位酶识别糖核苷酸：氟化底物、动力学和平衡†

  摘要：

  一系列选择性氟化和其他取代的 UDP- D-半乳糖衍生物已被评估为肺炎克雷伯氏菌UDP- D-吡喃半乳糖变位酶的底物。这种酶催化吡喃糖和呋喃糖形式的相互转化半乳糖作为其 UDP 加合物，是多种微生物感染的潜在药物靶点。我们表明，UDP- D-吡喃半乳糖的 2”-、3”-或 6”-羟基对底物结合和周转都不是必需的。然而，空间因子似乎在限制糖核苷酸底物的 C-2" 和 C-6" 处可容纳的取代范围方面发挥重要作用。尝试将 C-2" 立体化学从赤道反转为轴向，将D-半乳糖- 变为D-塔洛-构型，以尝试利用塔洛系列中平衡时较高百分比的呋喃糖，但没有底物周转.

  DOI：

  10.1039/b815549f

文献信息

• Rhodium-catalyzed reductive modification of pyrimidine nucleosides, nucleotide phosphates, and sugar nucleotides
  作者：Neil P.J. Price、Michael A. Jackson、Karl E. Vermillion、Judith A. Blackburn、Trina M. Hartman

  DOI：10.1016/j.carres.2019.107893

  日期：2020.2

  Nucleosides and nucleotides are a group of small molecule effectors and substrates which include sugar nucleotides, purine and pyrimidine-based nucleotide phosphates, and diverse nucleotide antibiotics. We previously reported that hydrogenation of the nucleotide antibiotic tunicamycin leads to products with reduced toxicity on eukaryotic cells. We now report the hydrogenation of diverse sugar nucleosides

  核苷和核苷酸是一组小分子效应子和底物，包括糖核苷酸，嘌呤和嘧啶基核苷酸磷酸以及各种核苷酸抗生素。我们以前曾报道过，核苷酸抗生素衣霉素的氢化作用会导致产物对真核细胞的毒性降低。现在我们报道各种糖核苷，核苷酸磷酸和嘧啶核苷酸的氢化。UDP糖和其他尿苷基和胸苷基核苷被定量还原为相应的5,6-二氢核苷。胞嘧啶嘧啶被还原，但是主要产物是由胞嘧啶环的脱氨基产生的相应的5，6-二氢尿苷基核苷。
• 一种淫羊藿次苷Ⅰ类化合物、衍生物、药物组合物及其应用
  申请人：广东金骏康生物技术有限公司

  公开号：CN109369748A

  公开（公告）日：2019-02-22

  本公开提供了一种淫羊藿次苷Ⅰ类化合物以及衍生物，其结构式如式I所示的化合物或式I所示化合物的立体异构体、几何异构体、互变异构体、氮氧化物、水合物、溶剂化物、代谢产物、药学上可接受的盐或前药，所述淫羊藿次苷Ⅰ类化合物以及衍生物的合成原料选自槲皮素、芹菜素、山奈酚、黄芩素、野黄芩素、白杨素、黄豆苷元、染料木素、异鼠李素、杨梅黄酮、木犀草素、漆黄素或淫羊藿素。通过化学合成和生物工程的方法可以让自然界中存在较高的黄酮化合物(如芹菜素、槲皮素等)合成生物效果更好、经济效益更高的淫羊藿次苷Ⅰ类化合物及其衍生物。
• An Ambidextrous Polyphenol Glycosyltransferase <i>Pa</i>GT2 from <i>Phytolacca americana</i>
  作者：Rakesh Maharjan、Yohta Fukuda、Naomichi Shimomura、Taisuke Nakayama、Yuta Okimoto、Koki Kawakami、Toru Nakayama、Hiroki Hamada、Tsuyoshi Inoue、Shin-ichi Ozaki

  DOI：10.1021/acs.biochem.0c00224

  日期：2020.7.14

  pharmaceutical industries. However, the ability of UGTs to accept and glycosylate a wide range of substrates is not clearly understood due to the existence of a large number of UGTs. PaGT2, a UGT from Phytolacca americana, can regioselectively glycosylate piceatannol but has low activity toward other stilbenoids. To elucidate the substrate specificity and catalytic mechanism, we determined the crystal structures

  尿苷二磷酸糖基转移酶（UGT）催化小的疏水化合物的糖基化。由于糖基化是改善疏水性化合物的稳定性和水溶性的宝贵工具，因此UGT在食品，化妆品和制药行业中的应用引起了人们的关注。然而，由于存在大量的UGT，尚未清楚地理解UGTs接受和糖基化多种底物的能力。Pa GT2，一种来自美国植物（Phytolacca americana）的UGT ，可以区域选择性地糖基化甲基吡啶（piceatannol），但对其他类胡萝卜素的活性较低。为了阐明底物特异性和催化机理，我们确定了Pa的晶体结构。GT2有无底物，并进行了分子对接研究。该结构揭示了与底物识别有关的关键残基，表明除了UGT（His18）中高度保守的催化组氨酸外，还存在非保守的催化残基（His81）。通过突变分析阐明了鉴定出的残基在底物识别和催化中的作用。此外，Cys142的结构指导突变为其他残基Ala，Phe和Gln可使Pa GT2以高区域选择性
• Molecular and Structural Characterization of a Promiscuous <i>C</i> ‐Glycosyltransferase from <i>Trollius chinensis</i>
  作者：Jun‐Bin He、Peng Zhao、Zhi‐Min Hu、Shuang Liu、Yi Kuang、Meng Zhang、Bin Li、Cai‐Hong Yun、Xue Qiao、Min Ye

  DOI：10.1002/anie.201905505

  日期：2019.8.12

  TcCGT1, which is initiated by the spontaneous deprotonation of the substrate. The spacious binding pocket explains the substrate promiscuity, and the binding pose of the substrate determines C‐ or O‐glycosylation activity. Site‐directed mutagenesis at two residues (I94E and G284K) switched C‐ to O‐glycosylation. TcCGT1 is the first plant CGT with a crystal structure and the first flavone 8‐C‐glycosyltransferase

  在本文中，探索了药用植物金莲花（Trollius chinensis）中新的C-糖基转移酶（CGT）TcCGT1的催化混杂性。TcCGT1可以有效和区域特异性地催化36种黄酮和其他类黄酮的8 C糖基化，还可以催化多种酚的O糖基化。TcCGT1与尿苷二磷酸酯复合的晶体结构以1.85Å的分辨率测定。分子对接揭示了TcCGT1催化机制的新模型，该模型由底物的自发去质子化引发。宽大的装订袋说明了基材的混杂性，并且基材的装订姿势决定了C或O糖基化活性。位点定向诱变在两个残基（I94E和G284K）切换Ç -到Ò -glycosylation。TcCGT1是第一个具有晶体结构的植物CGT，并且是第一个描述的黄酮8- C-糖基转移酶。这为设计有效的糖基化生物催化剂提供了基础。
• Genome-wide mapping of 5-hydroxymethylcytosine in embryonic stem cells
  作者：William A. Pastor、Utz J. Pape、Yun Huang、Hope R. Henderson、Ryan Lister、Myunggon Ko、Erin M. McLoughlin、Yevgeny Brudno、Sahasransu Mahapatra、Philipp Kapranov、Mamta Tahiliani、George Q. Daley、X. Shirley Liu、Joseph R. Ecker、Patrice M. Milos、Suneet Agarwal、Anjana Rao

  DOI：10.1038/nature10102

  日期：2011.5.19

  The modified DNA base 5-hydroxymethylcytosine (5hmC), sometimes called the sixth base, is present in the mammalian genome where it is generated by oxidation of 5-methylcytosine (5mC; the fifth base) by enzymes of the Tet family. Four papers in this issue, from the Helin, Zhang, Rao and Reik laboratories, respectively, report on the genome-wide distribution of Tet1 and/or 5hmC in mouse embryonic stem cells using the ChIP-seq technique. Links between Tet1 and transcription regulation — both activation and repression — are revealed. Anjana Rao and colleagues also describe two alternative methods with increased sensitivity for mapping single 5hmC bases. In the associated News & Views, Nathalie Véron and Antoine H. F. M. Peters discuss what these and other recent papers reveal about the role of Tet proteins in regulating DNA methylation and gene expression. 5-hydroxymethylcytosine (5hmC) is a modified base present at low levels in diverse cell types in mammals1,2,3,4,5. 5hmC is generated by the TET family of Fe(II) and 2-oxoglutarate-dependent enzymes through oxidation of 5-methylcytosine (5mC)1,2,4,5,6,7. 5hmC and TET proteins have been implicated in stem cell biology and cancer1,4,5,8,9, but information on the genome-wide distribution of 5hmC is limited. Here we describe two novel and specific approaches to profile the genomic localization of 5hmC. The first approach, termed GLIB (glucosylation, periodate oxidation, biotinylation) uses a combination of enzymatic and chemical steps to isolate DNA fragments containing as few as a single 5hmC. The second approach involves conversion of 5hmC to cytosine 5-methylenesulphonate (CMS) by treatment of genomic DNA with sodium bisulphite, followed by immunoprecipitation of CMS-containing DNA with a specific antiserum to CMS5. High-throughput sequencing of 5hmC-containing DNA from mouse embryonic stem (ES) cells showed strong enrichment within exons and near transcriptional start sites. 5hmC was especially enriched at the start sites of genes whose promoters bear dual histone 3 lysine 27 trimethylation (H3K27me3) and histone 3 lysine 4 trimethylation (H3K4me3) marks. Our results indicate that 5hmC has a probable role in transcriptional regulation, and suggest a model in which 5hmC contributes to the ‘poised’ chromatin signature found at developmentally-regulated genes in ES cells.

  经修饰的DNA碱基——5-羟甲基胞嘧啶(5hmC),有时被称为第六种碱基——存在于哺乳动物基因组中,它是由Ten结构的酶将第五种碱基5-甲基胞嘧啶(5mC)氧化而生成的。在最近的一期杂志中,来自Helin、Zhang、Rao和Reik实验室的四篇文章,分别报道了小鼠胚胎干细胞内Tet1和/或5hmC的全基因组分布,研究中使用的技术是染色质免疫沉淀-测序法(ChIP-seq)。文章揭示了Tet1与转录调控的关联——既包括活化也包括抑制,Anjana Rao与同事还提出了两种灵敏度更高的检测方法,用以对单碱基5hmC进行定位。在同期杂志的新闻与观点栏目中,Nathalie Véron和Antoine H. F. M. Peters对之前和这些文章一起发表的论文进行了讨论,论述了Tet蛋白在调控DNA甲基化和基因表达过程中所起的作用。5-羟甲基胞嘧啶(5hmC)是一种处于低水平的修饰碱基,在各类哺乳动物细胞中都有发现。5hmC是由TET家族的Fe(II)依赖型、2-氧戊二酸依赖型酶类通过氧化作用由5-甲基胞嘧啶(5mC)生成的。5hmC和TET蛋白已经被证明与干细胞生物学和癌症的发生具有关联,但关于5hmC全基因组分布的信息还不多。这里我们描述了两种全新且具有针对性的研究5hmC在基因组上位置的方法。第一种方法称为GLIB(葡糖基化,高碘酸盐氧化,生物素化),利用一系列酶法和化学手段,分离仅含少量5hmC的DNA短链。第二种方法是用亚硫酸氢盐处理基因组DNA,使其中的5hmC转化为胞嘧啶-5-亚甲砜(CMS),再利用特异性抗血清对含有CMS的DNA作免疫共沉淀。对含有5hmC的小鼠胚胎干细胞(ES)基因组进行高通量测序后我们发现,测序结果强烈富集于外显子位置和转录起始位点附近。在携带有组蛋白3赖氨酸27三甲基化(H3K27me3)和组蛋白3赖氨酸4三甲基化(H3K4me3)标记的基因上游启动子区,5hmC高度富集。我们的结果显示,5hmC很可能具有调控转录的功能,并提出了一种假设,即5hmC能够参与到ES干细胞中,赋予那些受发育调控的基因以"预备"的组蛋白特征。