thymidine triphosphate | 1112104-15-0

• 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: thymidine triphosphate
• 英文别名: TTP；TTP tetraanion；[[[(2R,3S,4R,5R)-3,4-dihydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-oxidophosphoryl]oxy-oxidophosphoryl] phosphate
• CAS: 1112104-15-0
• 化学式: C₁₀H₁₃N₂O₁₅P₃
• 分子量: 494.139
• InChiKey: RZCIEJXAILMSQK-JXOAFFINSA-J

计算性质

• 辛醇/水分配系数(LogP)：
  -6.1
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  270
• 氢给体数：
  3
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  thymidine triphosphate 、 α-D-glucose-1-phosphate 在 盐酸 、 recombinant Trypanosoma cruzi pyrophosphorylase 、 magnesium chloride 作用下， 以 水 为溶剂， 反应 0.25h， 生成 TDP-glucose
  参考文献：
  名称：

  Identification of a novel UDP-sugar pyrophosphorylase with a broad substrate specificity in Trypanosoma cruzi

  摘要：

  与宿主细胞相比，锥虫寄生虫合成的各种类型的聚糖是独一无二的。这些聚糖是寄生虫生存、入侵或躲避宿主免疫系统所必需的。合成这些聚糖需要核苷酸-糖（NDP-糖）的持续供应，但人们对这些 NDP-糖是如何制造和供应的知之甚少。本文报告了克氏锥虫的一个功能基因，该基因编码一种核苷酸转移酶，能够将不同类型的 1-磷酸和 NTP 糖转化为 NDP 糖。在正向反应中，该酶催化 UDP-葡萄糖、UDP-半乳糖、UDP-木糖和 UDP-葡萄糖醛酸在UTP 的存在下从各自的单糖 1-磷酸酯中生成 UDP-葡萄糖、UDP-半乳糖、UDP-木糖和 UDP-葡萄糖醛酸。该酶还能将 1-磷酸葡萄糖和 TTP 转化为 TDP-葡萄糖，但转化效率较低。该酶的活性需要二价离子（Mg2+ 或 Mn2+），在 pH 6.5 至 pH 8.0 之间和 30-42 ℃ 时活性很高。正向反应的表观 Km 值分别为 177 μM（1-磷酸葡萄糖）和 28.4 μM（UTP）。这种不寻常的寄生虫酶具有如此广泛的底物特异性，它的发现提示了一种可能在核苷酸-糖生物合成和调节寄生虫体内 NDP-糖库方面发挥重要作用的替代途径。

  DOI：

  10.1042/bj20100238

文献信息

• Zinc-cyclen coordination to UTP, TTP or pyrophosphate induces pyrene excimer emission
  作者：Florian Schmidt、Stefan Stadlbauer、Burkhard König

  DOI：10.1039/c0dt00001a

  日期：——

  Pyrene labelled Zn2+-cyclen 1 and bis-Zn2+-bis-cyclen 2 complexes were synthesized. The reversible coordination at physiological pH of Zn2+-cyclens to phosphate anions and to imide moieties, as present in thymine and uracil nucleotides, is well known. In the presence of analytes bearing a phosphate and an imide or two phosphate groups the formation of a ternary complex consisting of two pyrene-labelled

  yr 标记的 锌2+循环1和双锌2+合成了双双环2配合物。在生理pH下可逆配位锌2+-骑自行车到 磷酸盐 阴离子和酰亚胺部分，如 胸腺嘧啶 和 尿嘧啶核苷酸，是众所周知的。在存在带有磷酸盐和酰亚胺基团或两个磷酸盐基团的分析物的存在下，观察到形成了由两个pyr标记的金属配合物和分析物分子组成的三元配合物。配合物中labels标记的紧密邻近引起pyr准分子发射，这可以由无武装的眼睛观察到。由此，存在联合会， UDP协议， 双绞线 和 TTP在缓冲水溶液中的信号被发信号，而其他核苷酸则不能诱导准分子发射。用同样的方式锌2+-cycln-re用作发光化学传感器 PP我 和 1,6-二磷酸果糖 在水性缓冲液中。
• Biochemical and Structural Studies of Conserved Maf Proteins Revealed Nucleotide Pyrophosphatases with a Preference for Modified Nucleotides
  作者：Anatoli Tchigvintsev、Dmitri Tchigvintsev、Robert Flick、Ana Popovic、Aiping Dong、Xiaohui Xu、Greg Brown、Wenyun Lu、Hong Wu、Hong Cui、Ludmila Dombrowski、Jeong Chan Joo、Natalia Beloglazova、Jinrong Min、Alexei Savchenko、Amy A. Caudy、Joshua D. Rabinowitz、Alexey G. Murzin、Alexander F. Yakunin

  DOI：10.1016/j.chembiol.2013.09.011

  日期：2013.11

  Maf (for multicopy associated filamentation) proteins represent a large family of conserved proteins implicated in cell division arrest but whose biochemical activity remains unknown. Here, we show that the prokaryotic and eukaryotic Maf proteins exhibit nucleotide pyrophosphatase activity against 5-methyl-UTP, pseudo-UTP, 5-methyl-CTP, and 7-methyl-GTP, which represent the most abundant modified bases in all organisms, as well as against canonical nucleotides dTTP, UTP, and CTP. Overexpression of the Maf protein YhdE. in E. coli cells increased intracellular levels of dTMP and UMP, confirming that dTTP and UTP are the in vivo substrates of this protein. Crystal structures and site-directed mutagenesis of Maf proteins revealed the determinants of their activity and substrate specificity. Thus, pyrophosphatase activity of Maf proteins toward canonical and modified nucleotides might provide the molecular mechanism for a dual role of these proteins in cell division arrest and house cleaning.
• First Apyrase Splice Variants Have Different Enzymatic Properties
  作者：Annette Biederbick、Christian Kosan、Jürgen Kunz、Hans-Peter Elsässer

  DOI：10.1074/jbc.m001245200

  日期：2000.6

  LALP70 is a novel lysosomal membrane protein belonging to the apyrase protein family. The apyrase protein family comprises enzymes capable of cleaving nucleotidetri- and diphosphates in a calcium- or magnesium-dependent manner, not being altered by P-type, F-type, or V-type NTPase inhibitors. In this study we have cloned and sequenced the human LALP70 gene to deter mine the genomic structure. The gene is organized in 11 introns and 12 exons covering a genomic region of approximately 16 kilobase pairs. By fluorescence in, situ hybridization analysis, the hLALP70 gene was mapped to the human chromosome 8p21.1-p21.3. We further show that there is at least one alternatively spliced variant, hLALP70v, which can be generated via an alternative splice side at the 3'-end of exon 7, leading to a protein variant differing in 8 amino acids (VSFASSQQ). This is the first splice variant that has been described in the apyrase protein family. Reverse transcriptase polymerase chain reaction analysis showed an ubiquitous expression of both variants, with different relative mRNA expression levels in different tissues. Comparison of the enzymatic properties of the splice variants revealed a broader substrate specificity for hLALP70v with CTP, UDP, CDP, GTP, and GDP as preferred substrates, while hLALP70 utilized UTP and TTP preferentially. Furthermore, enzyme activity of hLALP70v was equally dependent on Ca2+ and Mg2+, being saturated already at 1 mM concentration. In contrast, hLALP70 enzymatic activity were unsaturated up to 10 mM Ca2+, while Mg2+ showed a saturation at already 1 mhz concentration with 2-3-fold lower enzymatic activity as observed with Ca2+. Our data suggest that the presence or absence of the 8-amino acid motif VSFASSQQ provoke differences in substrate specificity and divalent cation dependence of hLALP70/hLALP70v.
• Identification of a novel UDP-sugar pyrophosphorylase with a broad substrate specificity in <i>Trypanosoma cruzi</i>
  作者：Ting Yang、Maor Bar-Peled

  DOI：10.1042/bj20100238

  日期：2010.8.1

  The diverse types of glycoconjugates synthesized by trypanosomatid parasites are unique compared with the host cells. These glycans are required for the parasite survival, invasion or evasion of the host immune system. Synthesis of those glycoconjugates requires a constant supply of nucleotide-sugars (NDP-sugars), yet little is known about how these NDP-sugars are made and supplied. In the present paper, we report a functional gene from Trypanosoma cruzi that encodes a nucleotidyltransferase, which is capable of transforming different types of sugar 1-phosphates and NTP into NDP-sugars. In the forward reaction, the enzyme catalyses the formation of UDP-glucose, UDP-galactose, UDP-xylose and UDP-glucuronic acid, from their respective monosaccharide 1-phosphates in the presence of UTP. The enzyme could also convert glucose 1-phosphate and TTP into TDP-glucose, albeit at lower efficiency. The enzyme requires bivalent ions (Mg2+ or Mn2+) for its activity and is highly active between pH 6.5 and pH 8.0, and at 30–42 °C. The apparent Km values for the forward reaction were 177 μM (glucose 1-phosphate) and 28.4 μM (UTP) respectively. The identification of this unusual parasite enzyme with such broad substrate specificities suggests an alternative pathway that might play an essential role for nucleotide-sugar biosynthesis and for the regulation of the NDP-sugar pool in the parasite.

  与宿主细胞相比，锥虫寄生虫合成的各种类型的聚糖是独一无二的。这些聚糖是寄生虫生存、入侵或躲避宿主免疫系统所必需的。合成这些聚糖需要核苷酸-糖（NDP-糖）的持续供应，但人们对这些 NDP-糖是如何制造和供应的知之甚少。本文报告了克氏锥虫的一个功能基因，该基因编码一种核苷酸转移酶，能够将不同类型的 1-磷酸和 NTP 糖转化为 NDP 糖。在正向反应中，该酶催化 UDP-葡萄糖、UDP-半乳糖、UDP-木糖和 UDP-葡萄糖醛酸在UTP 的存在下从各自的单糖 1-磷酸酯中生成 UDP-葡萄糖、UDP-半乳糖、UDP-木糖和 UDP-葡萄糖醛酸。该酶还能将 1-磷酸葡萄糖和 TTP 转化为 TDP-葡萄糖，但转化效率较低。该酶的活性需要二价离子（Mg2+ 或 Mn2+），在 pH 6.5 至 pH 8.0 之间和 30-42 ℃ 时活性很高。正向反应的表观 Km 值分别为 177 μM（1-磷酸葡萄糖）和 28.4 μM（UTP）。这种不寻常的寄生虫酶具有如此广泛的底物特异性，它的发现提示了一种可能在核苷酸-糖生物合成和调节寄生虫体内 NDP-糖库方面发挥重要作用的替代途径。