Deoxyguanosine diphosphate | 914806-45-4

• 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: Deoxyguanosine diphosphate
• 英文别名: [[(2R,3S,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-oxidophosphoryl] phosphate
• CAS: 914806-45-4
• 化学式: C₁₀H₁₂N₅O₁₀P₂
• 分子量: 424.18
• InChiKey: CIKGWCTVFSRMJU-KVQBGUIXSA-K

计算性质

• 辛醇/水分配系数(LogP)：
  -4.3
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  237
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  adenosine 5'-triphosphate 、 Deoxyguanosine diphosphate 生成 adenosine 5'-diphosphate 、 dGTP
  参考文献：
  名称：

  酿酒酵母核苷二磷酸激酶：纯化，鉴定和底物特异性。

  摘要：

  核苷二磷酸激酶是一种酶，可将核苷二磷酸磷酸化为相应的三磷酸以进行核酸生物合成。在本交流中，我们描述了酵母中核苷二磷酸激酶的纯化和表征。通过十二烷基硫酸钠-聚丙烯酰胺凝胶分析，纯化的蛋白质似乎是均质的，分子量约为17,000-18,000。快速蛋白质液相色谱Superose 12凝胶过滤的估算结果表明，其天然分子量约为68,000至70,000。结果表明，酵母核苷二磷酸激酶由四个亚基组成。底物特异性研究表明，核苷二磷酸酯（NDP）作为磷酸盐受体的相对活性为dTDP大于CDP大于UDP大于dUDP大于GDP大于或等于dGDP大于dCDP大于dADP大于ADP ; 三磷酸供体的相对活性的顺序为：UTP大于dTTP大于CTP大于dCTP大于dATP大于ATP大于或等于dGTP大于GTP。已确定dTDP，dGDP，dCDP，dUDP，CDP和UDP的Km和Vm。速率常数研究表明，纯化的NDP激酶在较小程度上更喜欢使用dTDP（约800

  DOI：

  10.1016/0003-9861(91)90129-7
• 作为产物：
  描述：

  在 硫酸氢铵 、 recombinant hexahistidine-tagged Caenorhabditis elegans scavenger decapping enzyme 、 水 、 magnesium chloride 作用下， 生成 Deoxyguanosine diphosphate 、 7-methylguanosine 5'-monophosphate
  参考文献：
  名称：

  Structural requirements for Caenorhabditis elegans DcpS substrates based on fluorescence and HPLC enzyme kinetic studies

  摘要：

  The activity of the Caenorhabditis elegans scavenger decapping enzyme (DcpS) on its natural substrates and dinucleotide cap analogs, modified with regard to the nucleoside base or ribose moiety, has been examined. All tested dinucleotides were specifically cleaved between β‐ and γ‐phosphate groups in the triphosphate chain. The kinetic parameters of enzymatic hydrolysis (Km, Vmax) were determined using fluorescence and HPLC methods, as complementary approaches for the kinetic studies of C. elegans DcpS. From the kinetic data, we determined which parts of the cap structure are crucial for DcpS binding and hydrolysis. We showed that m32,2,7GpppG and m32,2,7GpppA are cleaved with higher rates than their monomethylated counterparts. However, the higher specificity of C. elegans DcpS for monomethylguanosine caps is illustrated by the lower Km values. Modifications of the first transcribed nucleotide did not affect the activity, regardless of the type of purine base. Our findings suggest C. elegans DcpS flexibility in the first transcribed nucleoside‐binding pocket. Moreover, although C. elegans DcpS accommodates bulkier groups in the N7 position (ethyl or benzyl) of the cap, both 2′‐O‐ and 3′‐O‐methylations of 7‐methylguanosine result in a reduction in hydrolysis by two orders of magnitude.

  DOI：

  10.1111/j.1742-4658.2010.07709.x

文献信息

• Chemical and enzymatic characterization of recombinant rabbit muscle pyruvate kinase
  作者：Christian Boehme、Frank Bieber、Julia Linnemann、Reinhard Breitling、Stefan Lorkowski、Siegmund Reissmann

  DOI：10.1515/hsz-2012-0334

  日期：2013.5.1

  synthesis of TTP via an enzymatic cascade reaction. The metalloenzyme PK shows pronounced promiscuity and therefore fits well to the conditions of this reaction. PK commonly used today is isolated from rabbit muscle. We cloned and expressed the respective open reading frame in Escherichia coli, purified, and characterized the His-tagged recombinant enzyme. The enzyme has an activity optimum at 37°C and

  摘要 胸苷三磷酸 (TTP) 的逐步合成在最后一步需要激酶进行磷酸化。因为使用磷酸烯醇式丙酮酸 (PEP) 作为底物的丙酮酸激酶 (PK) 可以再生三磷酸腺苷和磷酸化胸苷二磷酸，我们选择这种酶通过酶促级联反应合成 TTP。金属酶 PK 表现出明显的混杂性，因此非常适合该反应的条件。今天常用的PK是从兔肌肉中分离出来的。我们在大肠杆菌中克隆并表达了各自的开放阅读框，纯化并表征了带有 His 标签的重组酶。该酶在 37°C 和 7.4 至 7.8 的 pH 范围内具有最佳活性。Km 常数与分离的二磷酸腺苷 (ADP) 天然酶一致，为 0.37±0。02 毫米，PEP 为 0.07±0.01 毫米。重组酶在其底物特异性方面表现出以下范围：ADP>dADP>dGDP>dCDP>胸苷二磷酸(TDP)。它允许以高产率（高达 95%）将 TDP 磷酸化为 TTP。金属离子 Mg2+ 和 K+ 是完全酶活性所必需的。添加过渡金属离子如
• Gene <i>ytkD</i> of <i>Bacillus subtilis</i> Encodes an Atypical Nucleoside Triphosphatase Member of the Nudix Hydrolase Superfamily
  作者：WenLian Xu、Candice R. Jones、Christopher A. Dunn、Maurice J. Bessman

  DOI：10.1128/jb.186.24.8380-8384.2004

  日期：2004.12.15

  Gene ytkD of Bacillus subtilis , a member of the Nudix hydrolase superfamily, has been cloned and expressed in Escherichia coli . The purified protein has been characterized as a nucleoside triphosphatase active on all of the canonical ribo- and deoxyribonucleoside triphosphates. Whereas all other nucleoside triphosphatase members of the superfamily release inorganic pyrophosphate and the cognate nucleoside monophosphate, YtkD hydrolyses nucleoside triphosphates in a stepwise fashion through the diphosphate to the monophosphate, releasing two molecules of inorganic orthophosphate. Contrary to a previous report, our enzymological and genetic studies indicate that ytkD is not an orthologue of E. coli mutT .

  摘要 基因 ytkD 的 基因 ytkD 是 Nudix水解酶超家族的成员，已被克隆并在 大肠杆菌 .纯化后的蛋白质被鉴定为一种核苷三磷酸酶，对所有典型的核糖核苷和脱氧核糖核苷三磷酸酶都有活性。该超家族的所有其他核苷三磷酸酶成员都会释放出无机焦磷酸和同源的核苷单磷酸，而 YtkD 则以逐步的方式从二磷酸水解到单磷酸，释放出两分子无机正磷酸盐。与之前的报告相反，我们的酶学和遗传学研究表明 ytkD 不是 大肠杆菌 mutT .
• Identification and Characterization of a Unique Adenosine Kinase from <i>Mycobacterium tuberculosis</i>
  作者：Mary C. Long、Vincent Escuyer、William B. Parker

  DOI：10.1128/jb.185.22.6548-6555.2003

  日期：2003.11.15

  Adenosine kinase (AK) is a purine salvage enzyme that catalyzes the phosphorylation of adenosine to AMP. In Mycobacterium tuberculosis , AK can also catalyze the phosphorylation of the adenosine analog 2-methyladenosine (methyl-Ado), the first step in the metabolism of this compound to an active form. Purification of AK from M. tuberculosis yielded a 35-kDa protein that existed as a dimer in its native form. Adenosine (Ado) was preferred as a substrate at least 30-fold ( K _m = 0.8 ± 0.08 μM) over other natural nucleosides, and substrate inhibition was observed when Ado concentrations exceeded 5 μM. M. tuberculosis and human AKs exhibited different affinities for methyl-Ado, with K _m values of 79 and 960 μM, respectively, indicating that differences exist between the substrate binding sites of these enzymes. ATP was a good phosphate donor ( K _m = 1100 ± 140 μM); however, the activity levels observed with dGTP and GTP were 4.7 and 2.5 times the levels observed with ATP, respectively. M. tuberculosis AK activity was dependent on Mg ²⁺ , and activity was stimulated by potassium, as reflected by a decrease in the K _m and an increase in V _max for both Ado and methyl-Ado. The N-terminal amino acid sequence of the purified enzyme revealed complete identity with Rv2202c, a protein currently classified as a hypothetical sugar kinase. When an AK-deficient strain of M. tuberculosis (SRICK1) was transformed with this gene, it exhibited a 5,000-fold increase in AK activity compared to extracts from the original mutants. These results verified that the protein that we identified as AK was coded for by Rv2202c. AK is not commonly found in bacteria, and to the best of our knowledge, M. tuberculosis AK is the first bacterial AK to be characterized. The enzyme shows greater sequence homology with ribokinase and fructokinase than it does with other AKs. The multiple differences that exist between M. tuberculosis and human AKs may provide the molecular basis for the development of nucleoside analog compounds with selective activity against M. tuberculosis .

  摘要 腺苷激酶（AK）是一种嘌呤挽救酶，可催化腺苷磷酸化为 AMP。在 结核分枝杆菌中 中，AK 还能催化腺苷类似物 2-甲基腺苷（甲基-Ado）的磷酸化，这是这种化合物代谢为活性形式的第一步。从 结核杆菌 得到了一种 35 kDa 蛋白质，其原生形式为二聚体。腺苷（Ado）作为底物的优先级至少提高了 30 倍 ( K m = 0.8 ± 0.08 μM），当 Ado 浓度超过 5 μM 时，底物抑制作用就会出现。 结核杆菌 和人类 AK 对甲基-Ado 表现出不同的亲和力，其中 K m 值分别为 79 μM 和 960 μM，表明这些酶的底物结合位点之间存在差异。ATP 是一种良好的磷酸盐供体 ( K m = 1100 ± 140 μM）；然而，用 dGTP 和 GTP 观察到的活性水平分别是用 ATP 观察到的活性水平的 4.7 倍和 2.5 倍。 结核杆菌 AK 活性取决于 Mg 2+ 钾对其活性有刺激作用。 K m 的降低和 V 最大值 增加。纯化酶的 N 端氨基酸序列显示与 Rv2202c 蛋白完全一致，后者目前被归类为假定的糖激酶。当一株 AK 缺失的 结核杆菌 (SRICK1）时，其 AK 活性比原始突变体的提取物提高了 5000 倍。这些结果验证了我们确定的 AK 蛋白是由 Rv2202c 所编码。 据我们所知，AK 在细菌中并不常见、 结核杆菌 AK 是第一个被鉴定的细菌 AK。与其他 AK 相比，该酶与核糖激酶和果糖激酶的序列同源性更高。与其他 AK 相比，结核杆菌 AK 与核糖激酶和果糖激酶的序列同源性更高。 结核杆菌 和人类 AK 之间存在的多种差异可能为开发对结核杆菌具有选择性活性的核苷类似物提供了分子基础。 结核杆菌 .
• Crystal structures of GMP kinase in complex with ganciclovir monophosphate and Ap5G
  作者：G. Hible、P. Daalova、A.-M. Gilles、J. Cherfils

  DOI：10.1016/j.biochi.2006.04.002

  日期：2006.9

  GMPK in complex with ganciclovir-monophosphate (GCV-MP) and with a bi-substrate inhibitor, Ap5G. GCV-MP binds as GMP to the GMP-binding domain, which is identical in E. coli and human GMPKs, but unlike the natural substrate fails to stabilize the closed, catalytically-competent conformation of this domain. Comparison with GMP- and GDP-bound GMPK structures identifies the 2'hydroxyl of the ribose moiety

  鸟嘌呤单磷酸激酶（GMPK）通过催化GMP或dGMP的磷酸化，在协助抗病毒前药的激活或作为抗生素策略的候选者方面具有双重潜力。人GMPK是激活无环鸟苷类似物（如更昔洛韦）的必不可少的步骤，这需要有效的磷酸化，而来自细菌病原体的GMPK（该酶是必需的）是治疗抑制的潜在目标。在这里，我们分析了GMPK活性的两个方面，即大肠杆菌GMPK的晶体结构与更昔洛韦单磷酸酯（GCV-MP）和双底物抑制剂Ap5G的复合物。GCV-MP作为GMP与GMP结合结构域结合，这在大肠杆菌和人GMPK中是相同的，但与天然底物不同的是，它不能稳定封闭结构，该结构域的催化能力构象。与结合GMP和GDP的GMPK结构进行比较，可以确定核糖部分的2'羟基负责将GMP结合结构域钩在CORE结构域上。GCV-MP中缺少此羟基会损害活性构象的稳定性，并解释了为什么GCV-MP的磷酸化效率低于GMP，但与dGMP一样高。相反，Ap5
• The rice nuclear gene, <i>VIRESCENT 2</i>, is essential for chloroplast development and encodes a novel type of guanylate kinase targeted to plastids and mitochondria
  作者：Hiroki Sugimoto、Kensuke Kusumi、Ko Noguchi、Masahiro Yano、Atsushi Yoshimura、Koh Iba

  DOI：10.1111/j.1365-313x.2007.03251.x

  日期：2007.11

  Guanylate kinase (GK) is a critical enzyme in guanine nucleotide metabolism pathways, catalyzing the phosphorylation of (d)GMP to (d)GDP. Here we show that a novel gene, VIRESCENT 2 (V2), encodes a new type of GK (designated pt/mtGK) that is localized in plastids and mitochondria. We initially identified the V2 gene by positional cloning of the rice v2 mutant. The v2 mutant is temperature‐sensitive and develops chlorotic leaves at restrictive temperatures. The v2 mutation causes inhibition of chloroplast differentiation; in particular, it disrupts the chloroplast translation machinery during early leaf development [Sugimoto et al. (2004)Plant Cell Physiol. 45, 985]. In the bacterial and animal species studied to date, GK is localized in the cytoplasm and participates in maintenance of the guanine nucleotide pools required for many fundamental cellular processes. Phenotypic analysis of rice seedlings with RNAi knockdown of cytosolic GK (designated cGK) showed that cGK is indispensable for the growth and development of plants, but not for chloroplast development. Thus, rice has two types of GK, as does Arabidopsis, suggesting that higher plants have two types of GK. Our results suggest that, of the two types of GK, only pt/mtGK is essential for chloroplast differentiation.

  摘要鸟苷酸激酶（GK）是鸟嘌呤核苷酸代谢途径中的一种关键酶，可催化(d)GMP磷酸化为(d)GDP。在这里，我们发现一个新基因 VIRESCENT 2（V2）编码一种新型 GK（命名为 pt/mtGK），这种 GK 定位于质粒和线粒体中。我们最初是通过定位克隆水稻 v2 突变体来确定 V2 基因的。v2 突变体对温度敏感，在限制性温度下会出现叶片萎黄。v2 基因突变会抑制叶绿体分化，尤其是在叶片早期发育过程中破坏叶绿体翻译机制[Sugimoto 等（2004）PlaNT Cell Physiol.45，985]。在迄今研究的细菌和动物物种中，GK 定位于细胞质中，参与维持许多基本细胞过程所需的鸟嘌呤核苷酸池。用 RNAi 方法敲除细胞质 GK（称为 cGK）的水稻幼苗的表型分析表明，cGK 对植物的生长和发育不可或缺，但对叶绿体的发育却不可或缺。因此，水稻和拟南芥一样有两种类型的 GK，这表明高等植物有两种类型的 GK。我们的研究结果表明，在这两种 GK 中，只有 pt/mtGK 对叶绿体的分化是必不可少的。