α-D-mannose-1-phosphate

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: α-D-mannose-1-phosphate
• 英文别名: mannose-1-phosphate；Man1P；alpha-D-mannose 1-phosphate(2-)；[(2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] phosphate
• 化学式: C₆H₁₁O₉P
• 分子量: 258.122
• InChiKey: HXXFSFRBOHSIMQ-RWOPYEJCSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  -4
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  163
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  α-D-mannose-1-phosphate 生成 mannose 6-phosphate
  参考文献：
  名称：

  Among Multiple Phosphomannomutase Gene Orthologues, Only One Gene Encodes a Protein with Phosphoglucomutase and Phosphomannomutase Activities in Thermococcus kodakaraensis

  摘要：

  摘要 在嗜热古生菌Thermococcus kodakaraensis的基因组中发现了四个可被注释为磷甘露糖酶（PMM）基因（COG1109）的同源基因（TK1108、TK1404、TK1777和TK2185）。 热球菌 KOD1。我们之前发现 TK1777 实际上编码一种磷酸戊二酸酶。为了确定其余三个直向同源物中哪个编码磷酸葡聚糖突变酶（PGM），我们研究了 T. kodakaraensis KOD1 的 PGM 活性。 细胞中的 PGM 活性。 细胞中的 PGM 活性，并确定了负责这种活性的基因。异源基因表达以及重组蛋白的纯化和表征表明，TK1108编码的蛋白具有高水平的PGM活性（690 U mg -1 ）以及高水平 PMM 活性（401 U mg -1 ).对其余两个直向同源物的类似分析表明，它们的蛋白产物既不表现出 PGM 活性，也不表现出 PMM 活性。T. kodakaraensis 中 TK1108 的 PGM 活性和转录 T. kodakaraensis 的 PGM 活性和转录均高于以淀粉为原料的细胞。我们的研究结果清楚地表明，在柯达卡拉氏菌的四个 PMM 基因直向同源物中 中，只有一个基因 中，只有一个基因 TK1108 实际编码具有 PGM 和 PMM 活性的蛋白质。

  DOI：

  10.1128/jb.186.18.6070-6076.2004
• 作为产物：
  描述：

  4-O-beta-D-mannopyranosyl-N-acetyl-D-glucosamine 、 H3PO4 生成 α-D-mannose-1-phosphate 、 D-GlcNAc
  参考文献：
  名称：

  Discovery of β-1,4-d-Mannosyl-N-acetyl-d-glucosamine Phosphorylase Involved in the Metabolism of N-Glycans

  摘要：

  A gene cluster involved in N-glycan metabolism was identified in the genome of Bacteroides thetaiotaomicron VPI-5482. This gene cluster encodes a major facilitator superfamily transporter, a starch utilization system-like transporter consisting of a TonB-dependent oligosaccharide transporter and an outer membrane lipoprotein, four glycoside hydrolases (alpha-mannosidase, beta-N-acetylhexosaminidase, exo-alpha-sialidase, and endo-beta-N-acetylglucosaminidase), and a phosphorylase (BT1033) with unknown function. It was demonstrated that BT1033 catalyzed the reversible phosphorolysis of beta-1,4-D-mannosyl-N-acetyl-D-glucosamine in a typical sequential Bi Bi mechanism. These results indicate that BT1033 plays a crucial role as a key enzyme in the N-glycan catabolism where beta-1,4-D-mannosyl-N-acetyl-D-glucosamine is liberated from N-glycans by sequential glycoside hydrolase-catalyzed reactions, transported into the cell, and intracellularly converted into alpha-D-mannose 1-phosphate and N-acetyl-D-glucosamine. In addition, intestinal anaerobic bacteria such as Bacteroides fragilis, Bacteroides helcogenes, Bacteroides salanitronis, Bacteroides vulgatus, Prevotella denticola, Prevotella dentalis, Prevotella melaninogenica, Parabacteroides distasonis, and Alistipes finegoldii were also suggested to possess the similar metabolic pathway for N-glycans. A notable feature of the new metabolic pathway for N-glycans is the more efficient use of ATP-stored energy, in comparison with the conventional pathway where beta-mannosidase and ATP-dependent hexokinase participate, because it is possible to directly phosphorylate the D-mannose residue of beta-1,4-D-mannosyl-N-acetyl-D-glucosamine to enter glycolysis. This is the first report of a metabolic pathway for N-glycans that includes a phosphorylase. We propose 4-O-beta-D-mannopyranosyl-N-acetyl-D-glucosamine:phosphate alpha-D-mannosyltransferase as the systematic name and beta-1,4-D-mannosyl-N-acetyl-D-glucosamine phosphorylase as the short name for BT1033.

  DOI：

  10.1074/jbc.m113.469080

文献信息

• Phosphomannose isomerase/GDP-mannose pyrophosphorylase from Pyrococcus furiosus: a thermostable biocatalyst for the synthesis of guanidinediphosphate-activated and mannose-containing sugar nucleotides
  作者：Rahman M. Mizanur、Nicola L. B. Pohl

  DOI：10.1039/b822794b

  日期：——

  Herein we present an analysis of the chemical function of a recombinant bifunctional phosphomannose isomerase/GDP-mannose pyrophosphorylase (manC) from Pyrococcus furiosusDSM 3638 and its use in the synthesis of guanidinediphospho-hexoses and a range of nucleotidediphospho-mannoses. This enzyme is unusually promiscuous in both its nucleotide triphosphate (NTP) and sugar-1-phosphate acceptance. It accepts all five naturally occurring NTPs (ATP, CTP, GTP, dTTP and UTP) and a range of sugar-1-phosphates (glucose-, mannose-, galactose-, glucosamine-, N-acetylglucosamine- and fucose-1-phosphate). A truncated GDP-mannose pyrophosphorylase domain of the whole length enzyme showed almost 100-fold less sugar nucleotidyltransferase activity with only GTP and mannose 1-phosphate as substrates. The temperature stability and inherently broad substrate tolerance of this archaeal enzyme make it an effective reagent for the rapid chemoenzymatic synthesis of a range of natural and unnatural sugar nucleotides that are challenging to make by chemical means alone.

  在本文中，我们分析了来自 Pyrococcus furiosusDSM 3638 的重组双功能磷甘露糖异构酶/GDP-甘露糖焦磷酸化酶（manC）的化学功能，以及它在合成鸟苷酸二磷六糖和一系列核苷酸二磷甘露糖中的应用。这种酶在接受核苷酸三磷酸（NTP）和糖-1-磷酸方面都异常杂乱。它能接受所有五种天然存在的 NTP（ATP、CTP、GTP、dTTP 和 UTP）和一系列糖-1-磷酸（葡萄糖、甘露糖、半乳糖、葡萄糖胺、N-乙酰葡萄糖胺和岩藻糖-1-磷酸）。全长酶的截短 GDP-甘露糖焦磷酸化酶结构域在仅以 GTP 和 1-磷酸甘露糖为底物的情况下，糖核苷酸转移酶活性几乎降低了 100 倍。这种古菌酶的温度稳定性和固有的广泛底物耐受性使其成为一种有效的试剂，可用于快速化学合成一系列天然和非天然糖核苷酸，而这些糖核苷酸很难通过化学方法单独制造。
• Purification and characterization of phosphomannomutase/phosphoglucomutase from Pseudomonas aeruginosa involved in biosynthesis of both alginate and lipopolysaccharide
  作者：R W Ye、N A Zielinski、A M Chakrabarty

  DOI：10.1128/jb.176.16.4851-4857.1994

  日期：1994.8

  The algC gene from Pseudomonas aeruginosa has been shown to encode phosphomannomutase (PMM), an essential enzyme for biosynthesis of alginate and lipopolysaccharide (LPS). This gene was overexpressed under control of the tac promoter, and the enzyme was purified and its substrate specificity and metal ion effects were characterized. The enzyme was determined to be a monomer with a molecular mass of 50 kDa. The enzyme catalyzed the interconversion of mannose 1-phosphate (M1P) and mannose 6-phosphate, as well as that of glucose 1-phosphate (G1P) and glucose 6-phosphate. The apparent Km values for M1P and G1P were 17 and 22 microM, respectively. On the basis of Kcat/Km ratio, the catalytic efficiency for G1P was about twofold higher than that for M1P. PMM also catalyzed the conversion of ribose 1-phosphate and 2-deoxyglucose 6-phosphate to their corresponding isomers, although activities were much lower. Purified PMM/phosphoglucomutase (PGM) required Mg2+ for maximum activity; Mn2+ was the only other divalent metal that showed some activation. The presence of other divalent metals in addition to Mg2+ in the reaction inhibited the enzymatic activity. PMM and PGM activities could not be detected in nonmucoid algC mutant strain 8858 and in LPS-rough algC mutant strain AK1012, while they were present in the wild-type strains as well as in algC-complemented mutant strains. This evidence suggests that AlgC functions as PMM and PGM in vivo, converting phosphomannose and phosphoglucose in the biosynthesis of both alginate and LPS.

  Pseudomonas aeruginosa的algC基因已被证明编码磷酸甘露糖异构酶（PMM），这是合成藻酸和脂多糖（LPS）必需的酶。该基因在tac启动子的控制下过表达，并纯化了酶，对其底物特异性和金属离子效应进行了表征。酶被确定为分子量为50 kDa的单体。该酶催化甘露糖1-磷酸（M1P）和甘露糖6-磷酸以及葡萄糖1-磷酸（G1P）和葡萄糖6-磷酸之间的互变。M1P和G1P的表观Km值分别为17和22微米。根据Kcat/Km比值，G1P的催化效率约为M1P的两倍。PMM还催化核糖1-磷酸和2-去氧葡萄糖6-磷酸的转化为相应的异构体，但活性要低得多。纯化的PMM/磷酸葡萄糖异构酶（PGM）需要Mg2+才能达到最大活性；Mn2+是唯一另一个显示出一定激活作用的双价金属。反应中除Mg2+以外的其他双价金属的存在会抑制酶活性。在非粘液型algC突变株8858和LPS-粗型algC突变株AK1012中无法检测到PMM和PGM活性，而在野生型菌株以及algC补充突变株中存在。这些证据表明AlgC在体内作为PMM和PGM发挥作用，将磷酸甘露糖和磷酸葡萄糖转化为合成藻酸和LPS所需的底物。
• Among Multiple Phosphomannomutase Gene Orthologues, Only One Gene Encodes a Protein with Phosphoglucomutase and Phosphomannomutase Activities in <i>Thermococcus kodakaraensis</i>
  作者：Naeem Rashid、Tamotsu Kanai、Haruyuki Atomi、Tadayuki Imanaka

  DOI：10.1128/jb.186.18.6070-6076.2004

  日期：2004.9.15

  Four orthologous genes (TK1108, TK1404, TK1777, and TK2185) that can be annotated as phosphomannomutase (PMM) genes (COG1109) have been identified in the genome of the hyperthermophilic archaeon Thermococcus kodakaraensis KOD1. We previously found that TK1777 actually encodes a phosphopentomutase. In order to determine which of the remaining three orthologues encodes a phosphoglucomutase (PGM), we examined the PGM activity in T. kodakaraensis cells and identified the gene responsible for this activity. Heterologous gene expression and purification and characterization of the recombinant protein indicated that TK1108 encoded a protein with high levels of PGM activity (690 U mg ⁻¹ ), along with high levels of PMM activity (401 U mg ⁻¹ ). Similar analyses of the remaining two orthologues revealed that their protein products exhibited neither PGM nor PMM activity. PGM activity and transcription of TK1108 in T. kodakaraensis were found to be higher in cells grown on starch than in cells grown on pyruvate. Our results clearly indicate that, among the four PMM gene orthologues in T. kodakaraensis , only one gene, TK1108, actually encodes a protein with PGM and PMM activities.

  摘要 在嗜热古生菌Thermococcus kodakaraensis的基因组中发现了四个可被注释为磷甘露糖酶（PMM）基因（COG1109）的同源基因（TK1108、TK1404、TK1777和TK2185）。 热球菌 KOD1。我们之前发现 TK1777 实际上编码一种磷酸戊二酸酶。为了确定其余三个直向同源物中哪个编码磷酸葡聚糖突变酶（PGM），我们研究了 T. kodakaraensis KOD1 的 PGM 活性。 细胞中的 PGM 活性。 细胞中的 PGM 活性，并确定了负责这种活性的基因。异源基因表达以及重组蛋白的纯化和表征表明，TK1108编码的蛋白具有高水平的PGM活性（690 U mg -1 ）以及高水平 PMM 活性（401 U mg -1 ).对其余两个直向同源物的类似分析表明，它们的蛋白产物既不表现出 PGM 活性，也不表现出 PMM 活性。T. kodakaraensis 中 TK1108 的 PGM 活性和转录 T. kodakaraensis 的 PGM 活性和转录均高于以淀粉为原料的细胞。我们的研究结果清楚地表明，在柯达卡拉氏菌的四个 PMM 基因直向同源物中 中，只有一个基因 中，只有一个基因 TK1108 实际编码具有 PGM 和 PMM 活性的蛋白质。
• GDP-mannose pyrophosphorylase is a genetic determinant of ammonium sensitivity in <i>Arabidopsis thaliana</i>
  作者：Cheng Qin、Weiqiang Qian、Wenfeng Wang、Yue Wu、Chunmei Yu、Xinhang Jiang、Daowen Wang、Ping Wu

  DOI：10.1073/pnas.0806168105

  日期：2008.11.25

  Higher plant species differ widely in their growth responses to ammonium (NH ₄ ⁺ ). However, the molecular genetic mechanisms underlying NH ₄ ⁺ sensitivity in plants remain unknown. Here, we report that mutations in the Arabidopsis gene encoding GDP-mannose pyrophosphorylase (GMPase) essential for synthesizing GDP-mannose confer hypersensitivity to NH ₄ ⁺ . The in planta activities of WT and mutant GMPases all were inhibited by NH ₄ ⁺ , but the magnitude of the inhibition was significantly larger in the mutant. Despite the involvement of GDP-mannose in both l -ascorbic acid (AsA) and N-glycoprotein biosynthesis, defective protein glycosylation in the roots, rather than decreased AsA content, was linked to the hypersensitivity of GMPase mutants to NH ₄ ⁺ . We conclude that NH ₄ ⁺ inhibits GMPase activity and that the level of GMPase activity regulates Arabidopsis sensitivity to NH ₄ ⁺ . Further analysis showed that defective N-glycosylation of proteins, unfolded protein response, and cell death in the roots are likely important downstream molecular events involved in the growth inhibition of Arabidopsis by NH ₄ ⁺ .

  高等植物物种对铵（NH4+）的生长反应差异很大。然而，植物对NH4+敏感性的分子遗传机制仍然未知。在这里，我们报告了在合成GDP-甘露磷酸（GMPase）所必需的Arabidopsis基因编码的GDP-甘露磷酸焦磷酸酶（GMPase）的突变体会导致对NH4+的高敏感性。WT和突变体GMPases的植株内活性都被NH4+抑制，但突变体的抑制幅度显著更大。尽管GDP-甘露磷酸参与了L-抗坏血酸（AsA）和N-糖蛋白质的生物合成，但与GMPase突变体对NH4+的高敏感性相关的是根部的缺陷蛋白质糖基化，而不是AsA含量降低。我们得出结论，NH4+抑制GMPase活性，GMPase活性水平调节Arabidopsis对NH4+的敏感性。进一步分析表明，蛋白质的缺陷N-糖基化，未折叠蛋白质反应和根部细胞死亡可能是涉及Arabidopsis生长抑制的下游分子事件。
• Three New Nudix Hydrolases from Escherichia coli
  作者：Wenlian Xu、Christopher A. Dunn、Suzanne F. O'Handley、Denise L. Smith、Maurice J. Bessman

  DOI：10.1074/jbc.m603407200

  日期：2006.8

  Nudix (nucleoside diphosphate X) hydrolase superfamily have been cloned from Escherichia coli MG1655 and expressed. The proteins have been purified and identified as enzymes active on nucleoside diphosphate derivatives with the following specificities. Orf141 (yfaO) is a nucleoside triphosphatase preferring pyrimidine deoxynucleoside triphosphates. Orf153 (ymfB) is a nonspecific nucleoside tri- and

  已从大肠杆菌MG1655中克隆并表达了Nudix（核苷二磷酸X）水解酶超家族的三个成员。蛋白质已被纯化并鉴定为对核苷二磷酸酯衍生物具有活性的酶，具有以下特异性。Orf141（yfaO）是一种核苷三磷酸酶，优选嘧啶脱氧核苷三磷酸。Orf153（ymfB）是一种非特异性核苷三磷酸酶和二磷酸酶，通常从三磷酸盐而不是焦磷酸盐中释放无机正磷酸盐。Orf191（yffH）是一种高活性GDP-甘露糖焦磷酸酶。所有这三种酶都需要二价阳离子才能发挥活性，并且在碱性pH值下具有最佳活性，这是Nudix水解酶超家族的特征。讨论了Orf1.9（wcaH）是否是Nudix水解酶超家族的真正成员的问题。