inosine 5'-triphosphate | 86527-71-1

• 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: inosine 5'-triphosphate
• 英文别名: ITP tetraanion；[[[(2R,3S,4R,5R)-3,4-dihydroxy-5-(6-oxo-1H-purin-9-yl)oxolan-2-yl]methoxy-oxidophosphoryl]oxy-oxidophosphoryl] phosphate
• CAS: 86527-71-1
• 化学式: C₁₀H₁₁N₄O₁₄P₃
• 分子量: 504.137
• InChiKey: HAEJPQIATWHALX-KQYNXXCUSA-J

计算性质

• 辛醇/水分配系数(LogP)：
  -5.5
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  280
• 氢给体数：
  3
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  L-蛋氨酸 、 inosine 5'-triphosphate 在 potassium chloride 、 magnesium chloride 作用下， 以 aq. buffer 为溶剂， 生成
  参考文献：
  名称：

  用于差异甲基转移酶靶向的核苷修饰 AdoMet 类似物。

  摘要：

  甲基转移酶 (MTase) 使用 S-腺苷-L-甲硫氨酸 (AdoMet) 作为共底物来修饰多种生物分子。合成的 AdoMet 类似物是功能强大的工具，可在位点特异性地引入各种官能团，并表现出只能通过不同的 MTase 进行转化的潜力。扩大硫/硒原子处取代基的大小提供了 MTase 之间的选择性，但不足以区分混杂的 MTase。我们提出了一组核苷部分不同的 AdoMet 类似物 (NM-AdoMets)。这些 NM-AdoMet 是由以前未表征的甲硫氨酸腺苷转移酶 (MAT) 从甲硫氨酸和 ATP 类似物（如 ITP 和 N6-炔丙基-ATP）高效产生的。N6 修饰将三种代表性 MTase 的相对活性改变高达 13 倍，从而区分甲基转移的底物，并且还可以与烯丙基和炔丙基的转移相结合。

  DOI：

  10.1039/c9cc07807j
• 作为产物：
  描述：

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

  烟曲霉核苷二磷酸激酶的核苷选择性

  摘要：

  烟曲霉感染与抗真菌药耐药率呈令人不安的上升趋势。由于对烟曲霉繁殖的基本生物学和结构机理的了解有限，阻碍了开发新型抗真菌药的努力。NDK催化NTP的生物合成，DNA和DNA的组成部分。NDK是烟曲霉中的必不可少的酶，是新型抗真菌药的诱人靶标。NDK在嘌呤和嘧啶中均表现出跨物种的广泛底物特异性，但这类核苷酸在烟曲霉中的选择性NDK未知，阻碍了结构导向抑制剂的设计。解决了未结合和未结合NDP的NDK结构，并在存在各种NTP底物的情况下评估了NDK的活性。我们呈现了独特的底物结合模式的第一个实例，该模式由烟曲霉NDK特有的CDP和TDP采用，阐明了选择性的结构决定因素。对低聚状态的分析表明，烟曲霉NDK在未结合和与NDP结合状态均采用六聚体组装，这与以前的报道表明它是四聚体相反。动力学分析表明，ATP具有最大的周转率（321±33.0 s -1），特异性常数（626±110.0 m m -1 ·s

  DOI：

  10.1111/febs.15607

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。
• Purification and Properties of ATP Deaminase*from Microsporum audouini
  作者：SHIAU-TA CHUNG、Kò AIDA

  DOI：10.1093/oxfordjournals.jbchem.a128507

  日期：1967.1

  A method was described for the purification of ATP deaminase [ATP aminohydrolase, EG class 3.5.4] from wheat-bran koji of Microsporum audouiniThis enzyme was found to deaminate adenosine tetraphosphate, ADP, 5′AMP, ADP-ribose, ADP-glucose, dATP, dADP, dAMP, 3′, 5′cyclic AMP, NAD, FAD, CoA, and adenosine, as well as ATP. Adenine, 2′-AMP, and NADP were not attacked by this enzyme.The deaminatcd product of ATP was proved to be ITP.The stoichiometry and equilibrium of deamination were studied.The activation energy of the enzyme activity was found to be approximately 7, 300 calories.The optimal pH was 5.0 in acetate buffer.The Michaelis-Menten constant was calculated to be 4×10−5M at 30°C.

  描述了一种从麦麸曲霉菌（Microsporum audouini）的小麦麸曲中纯化ATP脱氨酶（ATP氨基水解酶，EG 3.5.4级）的方法。该酶被发现能够脱氨化四磷酸腺苷（ATP）、5′AMP、ADP-核糖、ADP-葡萄糖、dATP、dADP、dAMP、3′、5′环状AMP、NAD、FAD、CoA和腺苷，以及ATP。腺嘌呤、2′-AMP和NADP不受该酶的影响。ATP的脱氨产物被证明是ITP。对脱氨的化学计量和平衡进行了研究。发现酶活性的激活能约为7300卡。在醋酸缓冲液中，最佳pH值为5.0。在30°C时，Michaelis-Menten常数计算为4×10−5M。
• Crystal structure of human cytosolic phosphoenolpyruvate carboxykinase reveals a new GTP-binding site
  作者：Pete Dunten、Charles Belunis、Robert Crowther、Kurt Hollfelder、Ursula Kammlott、Wayne Levin、Hanspeter Michel、Gwendolyn B Ramsey、Amy Swain、David Weber、Stanley J Wertheimer

  DOI：10.1006/jmbi.2001.5364

  日期：2002.2

  We report crystal structures of the human enzyme phosphoenolpyruvate carboxykinase (PEPCK) with and without bound substrates. These structures are the first to be determined for a GTP-dependent PEPCK, and provide the first view of a novel GTP-binding site unique to the GTP-dependent PEPCK family. Three phenylalanine residues form the walls of the guanine-binding pocket on the enzyme's surface and,

  我们报告了人类酶磷酸烯醇丙酮酸羧激酶（PEPCK）的晶体结构，有和没有结合的底物。这些结构是第一个针对GTP依赖的PEPCK的结构，并提供了GTP依赖的PEPCK家族独有的新型GTP结合位点的第一个视图。三个苯丙氨酸残基形成酶表面上鸟嘌呤结合口袋的壁，最令人惊讶的是，苯丙氨酸侧链之一有助于酶对GTP的特异性。PEPCK催化代谢途径中的限速步骤，该代谢途径由乳酸和柠檬酸循环产生的其他前体产生葡萄糖。由于糖异生途径会导致II型糖尿病的空腹高血糖，因此PEPCK抑制剂可用于治疗糖尿病。
• Biochemical characterization of a novel hypoxanthine/xanthine dNTP pyrophosphatase from Methanococcus jannaschii
  作者：J. H. Chung

  DOI：10.1093/nar/29.14.3099

  日期：2001.7.15

  A novel dNTP pyrophosphatase, Mj0226 from Methanococcus jannaschii, which catalyzes the hydrolysis of nucleoside triphosphates to the monophosphate and PPi, has been characterized. Mj0226 protein catalyzes hydrolysis of two major substrates, dITP and XTP, suggesting that the 6-keto group of hypoxanthine and xanthine is critical for interaction with the protein. Under optimal reaction conditions the kcat /Km value for these substrates was ∼10 000 times that with dATP. Neither endonuclease nor 3′‐exonuclease activities were detected in this protein. Interestingly, dITP was efficiently inserted opposite a dC residue in a DNA template and four dNTPs were also incorporated opposite a hypoxanthine residue in template DNA by DNA polymerase I. Two protein homologs of Mj0226 from Escherichia coli and Archaeoglobus fulgidus were also cloned and purified. These have catalytic activities similar to Mj0226 protein under optimal conditions. The implications of these results have significance in understanding how homologous proteins, including Mj0226, act biologically in many organisms. It seems likely that Mj0226 and its homologs have a major role in preventing mutations caused by incorporation of dITP and XTP formed spontaneously in the nucleotide pool into DNA. This report is the first identification and functional characterization of an enzyme hydrolyzing non-canonical nucleotides, dITP and XTP.

  一种新型的dNTP焦磷酸酶Mj0226来自甲烷球菌（Methanococcus jannaschii），它催化核苷三磷酸水解为单磷酸和PPi。Mj0226蛋白催化两种主要底物dITP和XTP的水解，表明次黄嘌呤和黄嘌呤的6-酮基团对于与蛋白的相互作用至关重要。在最佳反应条件下，这些底物的kcat/Km值约为dATP的10000倍。在该蛋白中未检测到内切酶或3'外切酶活性。有趣的是，dITP被有效地插入DNA模板中dC残基的对面，并且四种dNTP也被DNA聚合酶I插入模板DNA中次黄嘌呤残基的对面。来自大肠杆菌和古生菌的Mj0226的两个同源蛋白也被克隆和纯化。在最佳条件下，它们的催化活性与Mj0226蛋白相似。这些结果对于理解包括Mj0226在内的同源蛋白在许多生物中的生物学作用具有重要意义。Mj0226及其同源蛋白似乎在防止dITP和XTP（在核苷酸池中自发形成）掺入DNA引起的突变方面起着重要作用。该报告首次鉴定了水解非典型核苷
• Identificaiton of the dITP- and XTP-Hydrolyzing Protein from Escherichia coli
  作者：Ji-Hyung Chung、Hyun-Young Park、Jong-Ho Lee、Yang-Soo Jang

  DOI：10.5483/bmbrep.2002.35.4.403

  日期：2002.7.31

  A hypothetical 21.0 kDa protein (ORF O197) from Escherichia coli K-12 was cloned, purified, and characterized. The protein sequence of ORF O197(termed EcO197) shares a 33.5% identity with that of a novel NTPase from Methanococcus jannaschii. The EcO197 protein was purified using Ni-NTA affinity chromatography, protease digestion, and gel filtration column. It hydrolyzed nucleoside triphosphates with an O6 atom-containing purine base to nucleoside monophosphate and pyrophosphate. The EcO197 protein had a strong preference for deoxyinosine triphosphate (dITP) and xanthosine triphosphate (XTP), while it had little activity in the standard nucleoside triphosphates (dATP, dCTP, dGTP, and dTTP). These aberrant nucleotides can be produced by oxidative deamination from purine nucleotides in cells; they are potentially mutagenic. The mutation protection mechanisms are caused by the incorporation into DNA of unwelcome nucleotides that are formed spontaneously. The EcO197 protein may function to eliminate specifically damaged purine nucleotide that contains the 6-keto group. This protein appears to be the first eubacterial dITP-and XTP-hydrolyzing enzyme that has been identified.

  研究人员对大肠杆菌K-12中一种假设的21.0 kDa蛋白（ORF O197）进行了克隆、纯化和特性分析。ORF O197（称为EcO197）的蛋白序列与甲烷球菌（Methanococcus jannaschii）中一种新型NTP酶的蛋白序列有33.5%的相似度。研究人员使用Ni-NTA亲和色谱、蛋白酶消化和凝胶过滤柱对EcO197蛋白进行了纯化。该蛋白可将含O6原子的嘌呤碱基核苷三磷酸水解为核苷单磷酸和焦磷酸。EcO197蛋白对脱氧肌苷三磷酸（dITP）和黄嘌呤三磷酸（XTP）有很强的亲和力，而对标准核苷三磷酸（dATP、dCTP、dGTP和dTTP）几乎没有活性。这些异常核苷酸可通过细胞中嘌呤核苷酸的氧化脱氨作用产生，具有潜在的诱变性。突变保护机制是由于DNA中掺入了自发形成的非期望核苷酸。EcO197蛋白可能具有消除特定受损嘌呤核苷酸的功能，这些受损核苷酸含有6-酮基。该蛋白