xanthosine 5'-monophosphate | 809239-68-7

• 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: xanthosine 5'-monophosphate
• 英文别名: XMP；9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(phosphonooxymethyl)oxolan-2-yl]purine-2,6-diolate
• CAS: 809239-68-7
• 化学式: C₁₀H₁₁N₄O₉P
• 分子量: 362.192
• InChiKey: DCTLYFZHFGENCW-UUOKFMHZSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  -4.2
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  198
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  xanthosine 5'-monophosphate 、 potassium chlorido[(6-carbamoylpyridine-2-carboxylato(2-))-κ³N¹,N⁶,O²]palladate(1-) 以 aq. phosphate buffer 、 重水 为溶剂， 生成
  参考文献：
  名称：

  2,6-二取代吡啶的Pd 2 +配合物与核苷5'-单磷酸酯的相互作用

  摘要：

  为了更多地了解金属离子介导的核酸碱基识别的基本原理，即六个6，2，6-二取代的吡啶的PdCl +配合物。吡啶-2，6-二甲酰胺，其N 2，N 6-二甲基和N 2，N 6-二异丙基衍生物，6-氨基甲酰基吡啶-2-羧酸，6-氨基甲基吡啶-2-甲酰胺及其N 2-甲基衍生物，制备了它们，并通过1 H NMR光谱在pH 7.2的D 2 O中研究了它们与核苷5'-单磷酸酯（NMP）的相互作用。核碱基内的结合位点基于Pd 2 +进行分配引起碱基部分质子共振化学位移的变化。通过比较络合和未络合的NMP的芳族和异头质子的强度，可以确定在不同浓度下参与单核或双核Pd 2 +络合物的NMP的摩尔分数。一些吡啶配合物在NMP之间显示出中等的区分度。

  DOI：

  10.1016/j.jinorgbio.2014.05.013
• 作为产物：
  描述：

  IMP 在 recombinant inosine 5'-monophosphate dehydrogenase from Mycobacterium tuberculosis 、 potassium chloride 、 水 、 nicotinamide adenine dinucleotide 、 1,4-二巯基-2,3-丁二醇 作用下， 以 aq. buffer 为溶剂， 生成 xanthosine 5'-monophosphate
  参考文献：
  名称：

  结核分枝杆菌IMP脱氢酶的 生化特性：动力学机制，金属活化和协同系统的证据

  摘要：

  来自核苷酸生物合成途径的酶是开发新型抗分枝杆菌剂的潜在靶标。结核分枝杆菌（Mt IMPDH）的肌苷5'-单磷酸（IMP）脱氢酶催化IMP氧化为XMP，同时将NAD +转化为NADH。在目前的工作中，已将guaB2编码的Mt IMPDH克隆，表达并纯化至同质。重组Mt IMPDH的亚单位分子量为54 775 Da，并且电感耦合等离子体发射光谱和火焰原子吸收光谱法鉴定出每个亚单位的K +离子。戊二醛交联的数据表明，山IMPDH主要以四聚体形式存在。稳态动力学表明，Mt IMPDH的最佳活性取决于一价阳离子（主要是K +）的存在。初始速度和产物抑制模式表明稳态有序的Bi Bi动力学机制，其中IMP首先结合，然后是NAD +结合，并且产物释放是有序的。氢化物转移似乎不是限制性的。pH速率曲线表明一个去质子化基团对于催化是必不可少的，并且p K值分别为7.5和9.0的基团对于NAD +捆绑。使用温度

  DOI：

  10.1039/c4ra02142h

文献信息

• The Effects of Removing the GAT Domain from E. coli GMP Synthetase
  作者：Jessica L. Abbott、Jordan M. Newell、Christine M. Lightcap、Mary E. Olanich、Danielle T. Loughlin、Melanie A. Weller、Gary Lam、Sidney Pollack、Walter A. Patton

  DOI：10.1007/s10930-006-9032-5

  日期：2006.12

  E. coli GMP synthetase (GMPS) catalyzes the conversion of XMP to GMP. Ammonia, generated in the amino-terminal glutamine amidotransferase (GAT) domain, is transferred by an unknown mechanism to the ATP-pyrophosphatase (ATPP) domain, where it attacks a highly reactive adenyl-XMP intermediate, leading to GMP formation. To study the structural requirements for the activity of E. coli GMPS, we used PCR to generate a protein expression construct that contains the ATPP domain as well as the predicted dimerization domain (DD). The ATPP/DD protein is active in solution, utilizing NH 4 + as an NH3 donor. Size-exclusion chromatography demonstrates a dimeric mass for the ATPP/ DD protein, providing the first evidence in solution for the structural organization of the intact GMPS. Kinetic characterization of the ATPP/DD domain protein provides evidence that the presence of the GAT domain can regulate the activity of the ATPP domain.

  大肠杆菌 GMP 合成酶（GMPS）催化 XMP 向 GMP 的转化。在氨基末端谷氨酰胺脒基转移酶（GAT）结构域中生成的氨通过一种未知的机制转移到 ATP-焦磷酸酶（ATPP）结构域中，在该结构域中，氨攻击高活性的腺嘌呤-XMP 中间体，导致 GMP 的形成。为了研究大肠杆菌 GMPS 活性的结构要求，我们利用 PCR 技术生成了一种蛋白质表达构建体，其中包含 ATPP 结构域和预测的二聚化结构域 (DD)。ATPP/DD 蛋白在溶液中具有活性，利用 NH 4 + 作为 NH3 供体。尺寸排阻色谱法证明了 ATPP/DD 蛋白的二聚质量，首次在溶液中证明了完整的 GMPS 的结构组织。ATPP/DD 结构域蛋白质的动力学特性分析表明，GAT 结构域的存在可以调节 ATPP 结构域的活性。
• Identification of novel diphenyl urea inhibitors of Mt-GuaB2 active against Mycobacterium tuberculosis
  作者：Veeraraghavan Usha、Sudagar S. Gurcha、Andrew L. Lovering、Adrian J. Lloyd、Athina Papaemmanouil、Robert C. Reynolds、Gurdyal S. Besra

  DOI：10.1099/mic.0.042549-0

  日期：2011.1.1

  In contrast with most bacteria, which harbour a single inosine monophosphate dehydrogenase (IMPDH) gene, the genomic sequence ofMycobacterium tuberculosisH37Rv predicts three genes encoding IMPDH:guaB1,guaB2andguaB3. These three genes were cloned and expressed inEscherichia colito evaluate functional IMPDH activity. Purified recombinant Mt-GuaB2, which uses inosine monophosphate as a substrate, was identified as the only active GuaB orthologue inM. tuberculosisand showed optimal activity at pH 8.5 and 37 °C. Mt-GuaB2 was inhibited significantlyin vitroby a panel of diphenyl urea-based derivatives, which were also potent anti-mycobacterial agents againstM. tuberculosisandMycobacterium smegmatis, with MICs in the range of 0.2–0.5 μg ml⁻¹. When Mt-GuaB2 was overexpressed on a plasmidin transinM. smegmatis, a diphenyl urea analogue showed a 16-fold increase in MIC. Interestingly, when Mt-GuaB orthologues (Mt-GuaB1 and 3) were also overexpressed on a plasmidin transinM. smegmatis, they also conferred resistance, suggesting that although these Mt-GuaB orthologues were inactivein vitro, they presumably titrate the effect of the inhibitory properties of the active compoundsin vivo.

  与大多数只携带一个次黄嘌呤单磷酸脱氢酶（IMPDH）基因的细菌不同，Mycobacterium tuberculosis H37Rv基因组序列预测了三个编码IMPDH的基因：guaB1、guaB2和guaB3。这三个基因被克隆并在Escherichia coli中表达，以评估其功能性IMPDH活性。纯化的重组Mt-GuaB2，它使用次黄嘌呤单磷酸作为底物，被确定为M. tuberculosis中唯一活性的GuaB同源物，并在pH 8.5和37℃下显示出最佳活性。Mt-GuaB2被一系列二苯基脲衍生物明显地in vitro抑制，这些衍生物也是对M. tuberculosis和Mycobacterium smegmatis的有效杀菌剂，MIC在0.2-0.5μg ml⁻¹范围内。当在转录子中过表达Mt-GuaB2于M. smegmatis中时，一种二苯基脲类似物的MIC增加了16倍。有趣的是，当Mt-GuaB同源物（Mt-GuaB1和3）也在转录子中过表达于M. smegmatis中时，它们也提供了抗性，这表明尽管这些Mt-GuaB同源物在in vitro中无活性，但它们可能在in vivo中调节活性化合物的抑制性能。
• MazG, a Nucleoside Triphosphate Pyrophosphohydrolase, Interacts with Era, an Essential GTPase in<i>Escherichia coli</i>
  作者：Junjie Zhang、Masayori Inouye

  DOI：10.1128/jb.184.19.5323-5329.2002

  日期：2002.10

  Era is an essential GTPase inEscherichia coli, and Era has been implicated in a number of cellular functions. Homologues of Era have been identified in various bacteria and some eukaryotes. Using theeragene as bait in the yeast two-hybrid system to screenE. coligenomic libraries, we discovered that Era interacts with MazG, a protein of unknown function which is highly conserved among bacteria. The direct interaction between Era and MazG was also confirmed in vitro, being stronger in the presence of GDP than in the presence of GTPγS. MazG was characterized as a nucleoside triphosphate pyrophosphohydrolase which can hydrolyze all eight of the canonical ribo- and deoxynucleoside triphosphates to their respective monophosphates and PP_i, with a preference for deoxynucleotides. AmazGdeletion strain ofE. coliwas constructed by replacing themazGgene with a kanamycin resistance gene. UnlikemutT, a gene for another conserved nucleotide triphosphate pyrophosphohydrolase that functions as a mutator gene, themazGdeletion did not result in a mutator phenotype inE. coli.

  摘要Era 是大肠杆菌（Escherichia coli）中一种重要的 GTP 酶，Era 与多种细胞功能有关。目前已在多种细菌和一些真核生物中发现了 Era 的同源物。我们利用酵母双杂交系统中的 Eeragene 作为诱饵筛选大肠杆菌基因组文库，发现 Era 与 MazG 相互作用，MazG 是一种功能未知的蛋白质，在细菌中高度保守。我们还在体外证实了 Era 与 MazG 之间的直接相互作用，这种作用在 GDP 存在时比在 GTPγS 存在时更强。MazG 被鉴定为一种核苷三磷酸焦磷酸水解酶，可将所有八种核糖核苷和脱氧核苷三磷酸水解为各自的单磷酸和 PPi，并偏好脱氧核苷酸。通过用卡那霉素抗性基因替换 AmazG 基因，构建了大肠杆菌 AmazG 基因缺失株。与作为突变基因的另一种保守的核苷酸三磷酸焦磷酸水解酶基因mutT不同，AmazG缺失并没有导致大肠杆菌出现突变表型。
• Crystal Structure of <i>Toxoplasma gondii</i> Hypoxanthine-Guanine Phosphoribosyltransferase with XMP, Pyrophosphate, and Two Mg²⁺ Ions Bound:  Insights into the Catalytic Mechanism^,
  作者：Annie Héroux、E. Lucile White、Larry J. Ross、Richard L. Davis、David W. Borhani

  DOI：10.1021/bi990508i

  日期：1999.11.1

  5-fold. The ternary complex crystallizes in space group C222(1) (a = 55.21 A, b = 112.25 A, and c = 144.28 A) with two subunits in the asymmetric unit; the HGPRT tetramer is completed by the application of 2-fold crystallographic symmetry. All active sites contain XMP ¿bound in a fashion similar to that of the guanosine 5'-monophosphate (GMP) and inosine 5'-monophosphate (IMP) complexes reported in

  刚体弓形虫次黄嘌呤-鸟嘌呤磷酸核糖基转移酶（HGPRT）-黄嘌呤5'-单磷酸（XMP）-焦磷酸-Mg（2+）三元复合物的晶体结构已确定为1. 60 A分辨率。这种双产物的过渡后状态结构是弓形虫HGPRT突变体（Asp150Ala或D150A）。与野生型刚地弓形虫HGPRT相比，D150A突变体的活性降低（次黄嘌呤，鸟嘌呤和黄嘌呤的k（cat）降低11倍，296倍和8.6倍）。嘌呤碱的米氏常数仅略有变化，而α-D-5-磷酸核糖基1-焦磷酸酯（PRPP）的米氏常数则降低了约6.5倍。三元复合物在空间群C222（1）中结晶（a = 55.21 A，b = 112.25 A，c = 144.28 A），并且在不对称单元中具有两个亚单元。HGPRT四聚体通过应用2倍晶体对称性完成。所有活性位点均含有XMP，其结合方式与先前文章中报道的鸟苷5'-单磷酸酯（GMP）和肌苷5'-单磷酸酯（IMP）络合物[Héroux，A
• 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