D-ribose-5-phosphate

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: D-ribose-5-phosphate
• 英文别名: ribose-5-phosphate；aldehydo-D-ribose 5-phosphate；[(2R,3R,4R)-2,3,4-trihydroxy-5-oxopentyl] phosphate
• 化学式: C₅H₉O₈P
• 分子量: 228.095
• InChiKey: PPQRONHOSHZGFQ-LMVFSUKVSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  -3.6
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  150
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  D-ribose-5-phosphate 生成 D-ribulose-5-phosphate
  参考文献：
  名称：

  来自大肠杆菌的 D-核糖-5-磷酸异构酶 B 也是一种功能性 D-阿洛糖-6-磷酸异构酶，而结核分枝杆菌酶则不是。

  摘要：

  D-核糖 5-磷酸 (R5P) 和 D-核酮糖-5-磷酸的相互转化是磷酸戊糖途径中的重要步骤。两种具有 R5P 异构酶活性的不相关酶首先在大肠杆菌中被鉴定，RpiA 和 RpiB。在这种生物体中，必需的 5 碳糖被认为是由 RpiA 加工的，而 RpiB 的主要作用被认为是罕见的 6 碳糖 D-阿洛糖-6-磷酸 (All6P) 和 D- 6-磷酸阿洛酮糖。在仅发现 RpiB 的结核分枝杆菌中，5 碳糖被认为是该酶的主要底物。在这里，我们展示了检查这两种生物的 RpiB 的 All6P 异构酶活性的动力学研究，并表明只有大肠杆菌酶才能有效地催化反应。相反，All6P 充当 M 的抑制剂。结核酶对 R5P 的作用。结核分枝杆菌酶与 All6P 和 5-deoxy-5-phospho-D-ribonohydroxamate（一种旨在模拟 6-碳糖的抑制剂）共结晶的 X 射线研究以及与大肠杆菌酶结

  DOI：

  10.1016/j.jmb.2008.06.090
• 作为产物：
  描述：

  D-glyceraldehyde 3-phosphate 、 sedoheptulose 7-phosphate 生成 D-ribose-5-phosphate 、 D-xylulose-5-phosphate
  参考文献：
  名称：

  Structure and Properties of an Engineered Transketolase from Maize

  摘要：

  通过南方杂交使用来自高粱（Sorghum bicolor）的异源探针，从玉米（Zea mays）的cDNA文库中克隆了编码质体转酮醇酶（TK）的基因。在大肠杆菌（Escherichia coli）中高水平表达了由玉米成熟TK和大肠杆菌硫氧还蛋白组成的重组融合蛋白，并用凝血酶切割，得到质体TK。与硫胺素焦磷酸盐结合的蛋白质被结晶，并通过分子替代法解决了其结构。该酶是一个C2对称的同源二聚体，与酵母（Saccharomyces cerevisiae）酶非常相似。每个亚基折叠成三个结构域。两个拓扑等价的活性位点位于亚基界面区域，并类似于酵母酶的活性位点。

  DOI：

  10.1104/pp.103.020982

文献信息

• Identification of protein-ribulosamine-5-phosphatase as human low-molecular-mass protein tyrosine phosphatase-A
  作者：Juliette Fortpied、Rita Gemayel、Didier Vertommen、Emile Van Schaftingen

  DOI：10.1042/bj20061485

  日期：2007.8.15

  Ribulosamines, which are substrates for the deglycating enzyme fructosamine-3-kinase-related protein, are presumably formed intracellularly through glycation of proteins with ribose 5-phosphate followed by dephosphorylation of resulting RN5Ps (ribulosamine 5-phosphates) by a putative RN5Pase (ribulosamine-5-phosphatase). Ribose 5-phosphate is known to be a potent glycating agent and we show in the present study that it reacts ∼10 and 80-fold more rapidly with protein than ribose and glucose respectively. We also show that tissue extracts and, most particularly, erythrocyte extracts contain a protein-RN5Pase. We have purified this enzyme from human erythrocytes to near homogeneity and shown it to correspond to LMWPTP-A [low-molecular-mass (‘weight’) protein tyrosine phosphatase-A]. Human recombinant LMWPTP-A displayed an RN5Pase activity that was higher than its tyrosine phosphatase activity, indicating that this phosphatase may participate in protein deglycation, a new form of protein repair.

  核糖胺是果糖胺-3-激酶相关蛋白脱糖酶的底物，它可能是通过蛋白质与 5-磷酸核糖发生糖化，然后由一种假定的 RN5Pase（核糖胺-5-磷酸酶）对由此产生的 RN5Ps（5-磷酸核糖胺）进行去磷酸化而在细胞内形成的。众所周知，5-磷酸核糖是一种强效糖化剂，我们在本研究中发现，它与蛋白质发生反应的速度分别比核糖和葡萄糖快 10 倍和 80 倍。我们还发现，组织提取物，尤其是红细胞提取物中含有一种蛋白质-RN5Pase。我们从人类红细胞中纯化出了这种接近均一的酶，并证明它与 LMWPTP-A [低分子质量（"重量"）蛋白酪氨酸磷酸酶-A]相对应。人重组 LMWPTP-A 的 RN5Pase 活性高于其酪氨酸磷酸酶活性，这表明这种磷酸酶可能参与了蛋白质的脱蛋白作用，这是一种新的蛋白质修复形式。
• Plant ribulosamine/erythrulosamine 3-kinase, a putative protein-repair enzyme
  作者：Juliette FORTPIED、Rita GEMAYEL、Vincent STROOBANT、Emile van SCHAFTINGEN

  DOI：10.1042/bj20041976

  日期：2005.6.15

  FN3K (fructosamine 3-kinase) is a mammalian enzyme that catalyses the phosphorylation of fructosamines, which thereby becomes unstable and detaches from proteins. The homologous mammalian enzyme, FN3K-RP (FN3K-related protein), does not phosphorylate fructosamines but ribulosamines, which are probably formed through a spontaneous reaction of amines with ribose 5-phosphate, an intermediate of the pentose–phosphate pathway and the Calvin cycle. We show in the present study that spinach leaf extracts display a substantial ribulosamine kinase activity (approx. 700 times higher than the specific activity of FN3K in erythrocytes). The ribulosamine kinase was purified approx. 400 times and shown to phosphorylate ribulose-ε-lysine, protein-bound ribulosamines and also, with higher affinity, erythrulose-ε-lysine and protein-bound erythrulosamines. Evidence is presented for the fact that the third carbon of the sugar portion is phosphorylated by this enzyme and that this leads to the formation of unstable compounds decomposing with half-lives of approx. 30 min at 37 °C (ribulosamine 3-phosphates) and 5 min at 30 °C (erythrulosamine 3-phosphates). This decomposition results in the formation of a 2-oxo-3-deoxyaldose and inorganic phosphate, with regeneration of the free amino group. The Arabidopsis thaliana homologue of FN3K/FN3K-RP was overexpressed in Escherichia coli and shown to have properties similar to those of the enzyme purified from spinach leaves. These results indicate that the plant FN3K/FN3K-RP homologue, which appears to be targeted to the chloroplast in many species, is a ribulosamine/erythrulosamine 3-kinase. This enzyme may participate in a protein deglycation process removing Amadori products derived from ribose 5-phosphate and erythrose 4-phosphate, two Calvin cycle intermediates that are potent glycating agents.

  FN3K（果糖胺 3-激酶）是一种哺乳动物酶，可催化果糖胺的磷酸化，从而使其变得不稳定并从蛋白质中分离出来。哺乳动物的同源酶 FN3K-RP（FN3K 相关蛋白）并不磷酸化果糖胺，而是磷酸化核糖胺，核糖胺可能是通过胺与 5-磷酸核糖（磷酸戊糖途径和卡尔文循环的中间体）的自发反应形成的。我们在本研究中发现，菠菜叶提取物显示出大量核糖胺激酶活性（比红细胞中 FN3K 的特异性活性高约 700 倍）。核糖激酶被纯化了约 400 倍，并被证明能使核酮糖-ε-赖氨酸、蛋白质结合的核糖胺以及亲和力更高的红酮糖-ε-赖氨酸和蛋白质结合的红酮胺磷酸化。有证据表明，糖部分的第三个碳会被这种酶磷酸化，从而形成不稳定的化合物，在 37 °C 下半衰期约为 30 分钟（3-核糖胺磷酸酯），在 30 °C 下半衰期约为 5 分钟（3-红豆杉胺磷酸酯）。分解的结果是形成 2-氧代-3-脱氧糖和无机磷酸盐，游离氨基再生。拟南芥 FN3K/FN3K-RP 的同源物在大肠杆菌中过度表达，结果表明其性质与从菠菜叶中纯化的酶相似。这些结果表明，植物 FN3K/FN3K-RP 同源物是一种核糖胺/赤藓酮胺 3- 激酶，在许多物种中似乎都以叶绿体为靶标。这种酶可能参与蛋白质脱糖过程，清除由 5-磷酸核糖和 4-磷酸赤藓糖（两种卡尔文循环中间产物，是强效糖化剂）产生的 Amadori 产物。
• Strain and Near Attack Conformers in Enzymic Thiamin Catalysis:  X-ray Crystallographic Snapshots of Bacterial Transketolase in Covalent Complex with Donor Ketoses Xylulose 5-phosphate and Fructose 6-phosphate, and in Noncovalent Complex with Acceptor Aldose Ribose 5-phosphate
  作者：Peter Asztalos、Christoph Parthier、Ralph Golbik、Martin Kleinschmidt、Gerhard Hübner、Manfred S. Weiss、Rudolf Friedemann、Georg Wille、Kai Tittmann

  DOI：10.1021/bi700844m

  日期：2007.10.1

  out-of-plane distortion of the C2-Calpha bond connecting the substrates' carbonyl with the C2 of the cofactor's thiazolium part. Both intermediates adopt very similar extended conformations in the active site with a perpendicular orientation of the scissile C2-C3 sugar bond relative to the thiazolium ring. The sugar-derived hydroxyl groups of the intermediates form conserved hydrogen bonds with one Asp side

  转酮醇酶是糖代谢中一种重要的硫胺素二磷酸依赖性酶，可催化2-碳二羟乙基片段在供体酮糖和受体醛糖之间的可逆转移。来自大肠杆菌的转酮醇酶的X射线结构与供体酮糖d-木酮糖5-磷酸（X5P）和d-果糖6-磷酸（F6P）的共价复合物在1.47 A和1.65 A的分辨率下显示出四面体的显着应变辅助因子糖加合物，其C2-Calpha键的面外变形为25-30度，将底物的羰基与辅助因子的噻唑鎓部分的C2连接起来。两种中间体均在活性位点采用非常相似的扩展构象，且可裂开的C2-C3糖键相对于噻唑环垂直。中间体的糖衍生的羟基与一个Asp侧链，His残基簇和辅因子的氨基嘧啶环的N4'形成保守的氢键。磷酸盐部分通过与Arg，His和Ser侧链的静电和氢键相互作用保持在适当位置。除辅因子的噻唑鎓部分外，在中间体形成过程中未观察到结构变化，表明活性位点已准备好进行催化。在X5P-硫胺和X5P-噻唑鎓模型上的DFT计算表明
• Structure and function of the transketolase from <i>Mycobacterium tuberculosis</i> and comparison with the human enzyme
  作者：Elizabeth Fullam、Florence Pojer、Terese Bergfors、T. Alwyn Jones、Stewart T. Cole

  DOI：10.1098/rsob.110026

  日期：2012.1

  The transketolase (TKT) enzyme in Mycobacterium tuberculosis represents a novel drug target for tuberculosis treatment and has low homology with the orthologous human enzyme. Here, we report on the structural and kinetic characterization of the transketolase from M. tuberculosis (TBTKT), a homodimer whose monomers each comprise 700 amino acids. We show that TBTKT catalyses the oxidation of donor sugars xylulose-5-phosphate and fructose-6-phosphate as well as the reduction of the acceptor sugar ribose-5-phosphate. An invariant residue of the TKT consensus sequence required for thiamine cofactor binding is mutated in TBTKT; yet its catalytic activities are unaffected, and the 2.5 Å resolution structure of full-length TBTKT provides an explanation for this. Key structural differences between the human and mycobacterial TKT enzymes that impact both substrate and cofactor recognition and binding were uncovered. These changes explain the kinetic differences between TBTKT and its human counterpart, and their differential inhibition by small molecules. The availability of a detailed structural model of TBTKT will enable differences between human and M. tuberculosis TKT structures to be exploited to design selective inhibitors with potential antitubercular activity.

  翻译结果如下： 转酮糖酶（TKT）是结核病治疗的一种新型药物靶标，在Mycobacterium tuberculosis中具有低同源性。在这里，我们报告了来自M. tuberculosis（TBTKT）的转酮糖酶的结构和动力学特征，它是一个由两个同源二聚体组成的，每个单体包含700个氨基酸。我们展示了TBTKT催化供体糖木糖-5-磷酸和果糖-6-磷酸的氧化以及受体糖核糖-5-磷酸的还原。TBTKT中TKT共识序列的一个不变残基，该残基对硫胺素辅因子结合是必需的，已经发生突变，但其催化活性未受影响，全长TBTKT的2.5 Å分辨率结构提供了解释。我们揭示了人类和分枝杆菌TKT酶之间的关键结构差异，这些差异影响了底物和辅因子的识别和结合。这些变化解释了TBTKT和其人类同源体之间的动力学差异，以及它们被小分子抑制的差异。TBTKT详细的结构模型的可用性将使人类和M. tuberculosis TKT结构之间的差异被利用来设计具有潜在抗结核活性的选择性抑制剂。
• Transketolase a of Escherichia coli K12. Purification and Properties of the Enzyme from Recombinant Strains
  作者：Georg A. Sprenger、Ulrich Schorken、Gerda Sprenger、Hermann Sahm

  DOI：10.1111/j.1432-1033.1995.0525h.x

  日期：1995.6

  U/mg. Km values for the substrates xylulose 5-phosphate and ribose 5-phosphate were 160 microM and 1.4 mM, respectively. Km values for the other physiological substrates of transketolase A were 90 microM for erythrose 4-phosphate (best acceptor substrate), 2.1 mM for D,L-glyceraldehyde 3-phosphate, 1.1 mM for fructose 6-phosphate, and 4 mM for sedoheptulose 7-phosphate. Hydroxypyruvate served as alternative

  从在pUC19衍生的质粒上携带同源克隆的tktA基因的重组大肠杆菌K12细胞中纯化转酮醇酶A使其具有明显的同质性。与野生型细胞中<0.1 U / mg或≤0.1 U / mg相比，这些重组细胞在粗提取物中的转酮醇酶活性高达9.7 U / mg。通过连续的硫酸铵沉淀和两个阴离子交换色谱步骤（Q-Sepharose FF，Fractogel EMD-DEAE色谱柱）从重组菌株的粗提物中纯化转酮醇酶A，并在SDS / PAGE上提供明显均一的蛋白带。通过凝胶过滤色谱法判断，该酶的活性形式和无顶形式的分子量均为145,000 Da（+/- 10,000 Da）。在SDS / PAGE上确定了73,000 Da（+/- 2000 Da）的亚基，因此，转酮醇酶A最有可能形成同型二聚体。蛋白质的N端氨基酸测序验证了与克隆基因tktA的同一性。在最佳pH（50 mM甘氨酰甘氨酸，pH 8.5）于30摄氏度