pseudouridine 5’-monophosphate | 1157-60-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: pseudouridine 5’-monophosphate
• 英文别名: 1,4-Anhydro-1-(2,4-dioxidopyrimidin-5-yl)-5-O-phosphonopentitol；5-[(2S,3R,4S,5R)-3,4-dihydroxy-5-(phosphonooxymethyl)oxolan-2-yl]pyrimidine-2,4-diolate
• CAS: 1157-60-4
• 化学式: C₉H₁₁N₂O₉P
• 分子量: 322.168
• InChiKey: MOBMOJGXNHLLIR-GBNDHIKLSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  -4.6
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  180
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  pseudouridine 5’-monophosphate 在 Quick CIP phosphatase 作用下， 以69.7 mg的产率得到假尿苷
  参考文献：
  名称：

  假尿苷的半酶法合成

  摘要：

  RNA分子的修饰对其结构和功能有显着影响。最常见的修饰之一是从尿苷异构化为假尿苷。尽管其在天然 RNA 序列中普遍存在，但由于立体化学要求和反应步骤对水分的敏感性，假尿苷的有机合成一直具有挑战性。在此，开发了一条以5'-磷酸腺苷和尿嘧啶为起始原料，在假尿苷单磷酸糖苷酶催化下进行逆反应合成假尿苷的半酶法合成路线。该合成路线只有三个步骤，β-假尿苷的总产率为68.4%。

  DOI：

  10.1016/j.bmcl.2021.128105
• 作为产物：
  描述：

  5'-腺嘌呤核苷酸 在 盐酸 、 manganese(II) chloride tetrahydrate 、 ΨMP glycosidase 作用下， 以 水 为溶剂， 反应 25.0h， 生成 pseudouridine 5’-monophosphate
  参考文献：
  名称：

  假尿苷的半酶法合成

  摘要：

  RNA分子的修饰对其结构和功能有显着影响。最常见的修饰之一是从尿苷异构化为假尿苷。尽管其在天然 RNA 序列中普遍存在，但由于立体化学要求和反应步骤对水分的敏感性，假尿苷的有机合成一直具有挑战性。在此，开发了一条以5'-磷酸腺苷和尿嘧啶为起始原料，在假尿苷单磷酸糖苷酶催化下进行逆反应合成假尿苷的半酶法合成路线。该合成路线只有三个步骤，β-假尿苷的总产率为68.4%。

  DOI：

  10.1016/j.bmcl.2021.128105

文献信息

• ON THE BIOSYNTHESIS OF PSEUDOURIDINE AND OF PSEUDOURIDYLIC ACID IN AGROBACTERIUM TUMEFACIENS
  作者：T. Suzuki、R. M. Hochster

  DOI：10.1139/o66-029

  日期：1966.2.1

  Crude extracts prepared from the plant tumor inducing organism Agrobacterium tumefaciens were shown to convert uracil and D-ribose-5-phosphate to pseudouridine in stoichiometric amounts. The addition of the nucleotidase inhibitor sodium arsenate altered the course of the reactions involved in such a way that pseudouridylic acid became the product. Under these conditions, the latter was formed in the same relative concentrations as pseudouridine in experiments without inhibitor.The direct synthesis of pseudouridylic acid from the above precursors was found to be catalyzed by an enzyme which has been tentatively designated as "pseudouridylic acid synthetase". This enzyme was separated from the nucleotidase and purified 80-fold. Parameters such as pH optimum, required ion concentration, and Michaelis constants were determined.The data presented in this paper permit the first description of the biosynthetic pathway for pseudouridylic acid and for pseudouridine in a bacterium.

  从植物肿瘤诱导菌Agrobacterium tumefaciens制备的粗提取物被证明能够将尿嘧啶和D-核糖-5-磷酸转化为假尿嘧啶，其比例相等。核苷酸酶抑制剂砷酸钠的加入改变了反应的进程，使假尿嘧啶酸成为产物。在这些条件下，后者的相对浓度与没有抑制剂的实验中假尿嘧啶相同。从上述前体直接合成假尿嘧啶酸的发现是由一种酶催化的，这种酶暂时被称为“假尿嘧啶酸合成酶”。这种酶已经与核苷酸酶分离并纯化了80倍。确定了pH最适值、所需离子浓度和Michaelis常数等参数。本文介绍的数据允许首次描述假尿嘧啶酸和假尿嘧啶在细菌中的生物合成途径。
• <i>HDHD1</i>, which is often deleted in X-linked ichthyosis, encodes a pseudouridine-5′-phosphatase
  作者：Alice Preumont、Rim Rzem、Didier Vertommen、Emile Van Schaftingen

  DOI：10.1042/bj20100174

  日期：2010.10.15

  Pseudouridine, the fifth-most abundant nucleoside in RNA, is not metabolized in mammals, but is excreted intact in urine. The purpose of the present work was to search for an enzyme that would dephosphorylate pseudouridine 5′-phosphate, a potential intermediate in RNA degradation. We show that human erythrocytes contain a pseudouridine-5′-phosphatase displaying a Km ≤ 1 μM for its substrate. The activity of the partially purified enzyme was dependent on Mg2+, and was inhibited by Ca2+ and vanadate, suggesting that it belonged to the ‘haloacid dehalogenase’ family of phosphatases. Its low molecular mass (26 kDa) suggested that this phosphatase could correspond to the protein encoded by the HDHD1 (haloacid dehalogenase-like hydrolase domain-containing 1) gene, present next to the STS (steroid sulfatase) gene on human chromosome Xp22. Purified human recombinant HDHD1 dephosphorylated pseudouridine 5′-phosphate with a kcat of 1.6 s−1, a Km of 0.3 μM and a catalytic efficiency at least 1000-fold higher than that on which it acted on other phosphate esters, including 5′-UMP. The molecular identity of pseudouridine-5′-phosphatase was confirmed by the finding that its activity was negligible (&lt;10% of controls) in extracts of B-cell lymphoblasts or erythrocytes from X-linked ichthyosis patients harbouring a combined deletion of the STS gene (the X-linked ichthyosis gene) and the HDHD1 gene. Furthermore, pseudouridine-5′-phosphatase activity was 1.5-fold higher in erythrocytes from women compared with men, in agreement with the HDHD1 gene undergoing only partial inactivation in females. In conclusion, HDHD1 is a phosphatase specifically involved in dephosphorylation of a modified nucleotide present in RNA.

  伪尿嘧啶是 RNA 中含量排名第五的核苷，在哺乳动物体内不进行代谢，而是完整地随尿液排出体外。本研究的目的是寻找一种能使假尿苷-5′-磷酸脱磷酸化的酶，假尿苷-5′-磷酸是 RNA 降解的潜在中间产物。我们发现人类红细胞中含有一种假尿嘧啶-5′-磷酸酶，其底物的 Km ≤ 1 μM。部分纯化的酶的活性依赖于 Mg2+，并受到 Ca2+和钒酸盐的抑制，这表明它属于 "卤酸脱卤酶 "磷酸酶家族。它的低分子质量（26 kDa）表明，这种磷酸酶可能对应于 HDHD1（含卤酸脱卤酶样水解酶结构域 1）基因编码的蛋白质，该基因位于人类染色体 Xp22 上的 STS（类固醇硫酸化酶）基因旁。纯化的人类重组 HDHD1 可使假尿苷-5′-磷酸脱磷酸化，其 kcat 为 1.6 s-1，Km 为 0.3 μM，催化效率比其对其他磷酸酯（包括 5′-UMP）的催化效率至少高 1000 倍。假尿嘧啶-5′-磷酸酶的分子特性得到了证实，因为在携带 STS 基因（X 连锁鱼鳞病基因）和 HDHD1 基因联合缺失的 X 连锁鱼鳞病患者的 B 细胞淋巴细胞或红细胞提取物中，假尿嘧啶-5′-磷酸酶的活性可以忽略不计（&lt;对照组的 10%）。此外，与男性相比，女性红细胞中假尿苷-5′-磷酸酶的活性高出1.5倍，这与女性HDHD1基因仅部分失活有关。总之，HDHD1 是一种磷酸酶，专门参与 RNA 中修饰核苷酸的去磷酸化作用。
• 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.
• Pseudouridine Monophosphate Glycosidase: A New Glycosidase Mechanism
  作者：Siyu Huang、Nilkamal Mahanta、Tadhg P. Begley、Steven E. Ealick

  DOI：10.1021/bi3006829

  日期：2012.11.13

  Pseudouridine (Psi), the most abundant modification in,RNA, is synthesized in situ using Psi synthase. Recently, a pathway for the degradation of P was described [Preumont, A., Snoussi, K., Stroobant; V., Collet, J. F., and Van Schaftingen, E. (2008) J. Biol. Chem. 283, 25238-25246]. In this pathway, Psi is first converted to Psi 5'-monophosphate (Psi MP) by Psi kinase and then Psi MP is degraded by Psi MP glycosidase to uracil and ribose 5-phosphate. Psi MP glycosidase is the first example of a mechanistically characterized enzyme. that cleaves a C-C glycosidic.bond. Here we report X-ray crystal structures of Escherichia colt Psi MP glycosidase and a complex of the K166A mutant with Psi MP. We also report the structures of a ring-opened ribose 5-phosphate adduct and a ring-opened ribose. Psi MP adduct. These structures provide four snapshots along the reaction coordinate. The structural studies suggested that the reaction utilizes a Lys166 adduct during catalysis.,Biochemical and mass spectrometry data further confirmed the existence of a lysine adduct. We used site directed mutagenesis combined with kinetic analysis to identify roles for specific active site residues. Together, these data suggest that Psi MP glycosidase catalyzes the cleavage of the C-C glycosidic bond through a novel ribose ring-opening mechanism.
• HEINRIKSON R.L.; GOLDWASSER E., J Biol Chem, 1964, 0021-9258, 1177-87
  作者：HEINRIKSON R.L.、GOLDWASSER E.

  DOI：——

  日期：——