D-glycero-D-manno-heptopyranose 1α,7-bisphosphate | 1181631-26-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: D-glycero-D-manno-heptopyranose 1α,7-bisphosphate
• 英文别名: D-glycero-D-manno-heptose 1α,7-bisphosphate；D-glycero-α-D-mannoheptose 1,7-biphosphate；H1α,7bisP；D-glycero-alpha-D-manno-heptose 1,7-bisphosphate；[(2R)-2-hydroxy-2-[(2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-phosphonooxyoxan-2-yl]ethyl] dihydrogen phosphate
• CAS: 1181631-26-4
• 化学式: C₇H₁₆O₁₃P₂
• 分子量: 370.144
• InChiKey: LMTGTTLGDUACSJ-ZUHYCWGWSA-N

物化性质

• 沸点：
  790.3±70.0 °C(Predicted)
• 密度：
  2.05±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -5.4
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  224
• 氢给体数：
  8
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  D-glycero-D-manno-heptopyranose 1α,7-bisphosphate 在 Escherichia coli D-glycero-D-manno-heptose 1β,7-bisphosphate phosphatase C109A mutant 、 水 、 magnesium chloride 作用下， 生成 (D-glycero-α-D-manno-Heptopyranosyl)dihydrogenphosphat
  参考文献：
  名称：

  Structural Determinants of Substrate Recognition in the HAD Superfamily Member d-glycero-d-manno-Heptose-1,7-bisphosphate Phosphatase (GmhB),

  摘要：

  The haloalkanoic acid dehalogenase (HAD) enzyme superfamily is the largest family of phosphohydrolases. In HAD members, the structural elements that provide the binding interactions that support substrate specificity are separated from those that orchestrate catalysis. For most HAD phosphatases, a cap domain functions in substrate recognition. However, for the HAD phosphatases that lack a cap domain, an alternate strategy for substrate selection must be operative. One such HAD phosphatase, GmhB of the HisB Subfamily, was selected for structure-function. analysis. Herein, the X-ray crystallographic structures of Escherichia coli GmhB in the apo form (1.6 angstrom resolution), in a complex with Mg2+ and orthophosphate (1.8 angstrom resolution), and in a complex with Mg2+ and D-glycero-D-manno-heptose 1 beta,7-bisphosphate (2.2 angstrom resolution) were determined, in addition to the Structure of Bordetella bronchiseptica GmhB bound to Mg2+ and orthophosphate (1.7 angstrom resolution). The Structures show that in place of a cap domain, the GmhB catalytic site is elaborated by three peptide inserts or loops that pack to form a concave, semicircular surface around the substrate leaving group. Structure-guided kinetic analysis of site-directed mutants was conducted in parallel with a bioinformatics study of sequence diversification within (lie HisB subfamily to identify loop residues that serve as substrate recognition elements and that distinguish GmhB from its subfamily counterpart, the histidinol-phosphate phosphatase domain of HisB. We show that GmhB and the histidinol-phosphate phosphatase domain use the same design of three Substrate recognition loops inserted into the cap domain yet, through selective residue usage on the loops, have achieved unique substrate specificity and thus novel biochemical function.

  DOI：

  10.1021/bi902019q
• 作为产物：
  描述：

  (2S,3S,4S,5S,6S)-3,4,5-tris(phenylmethoxy)-6-prop-2-enoxyoxane-2-carbaldehyde 在 咪唑 、 4-二甲氨基吡啶 、 (1,5-cyclooctadiene)[bis(methyldiphenylphosphine)]iridium(I) hexafluorophosphate 、 10 wt% Pd(OH)2 on carbon 、 四丁基氟化铵 、 氢气 、 四丁基碘化铵 、 sodium hydride 、 三乙胺 、 potassium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 100.0 ℃ 、506.66 kPa 条件下， 反应 104.0h， 生成 D-glycero-D-manno-heptopyranose 1α,7-bisphosphate
  参考文献：
  名称：

  d-甘油-d-甘露聚糖-庚糖1,7-二磷酸酯的化学合成及其调节NF-κB活化能力的评估

  摘要：

  d -甘油基- d -甘露-Heptose 1,7-二磷酸（HBP）是庚糖残基的前体在革兰氏阴性细菌膜表面糖蛋白和糖脂中。最近报道，HBPβ-异头物是一种病原体相关分子模式（PAMP），可调节TIFA依赖性免疫。在这里，我们报道了HBPα-和β-端基异构体的化学合成，该反应突出了通过Corey-Chaykovsky反应的C-7碳同系物，以及使用Mitsunobu反应在端基异构体位置引入了磷酸基团。此外，NF-κB报告基因检测表明，HBPβ-异头物激活了NF-κB信号传导途径。

  DOI：

  10.1021/acs.orglett.7b01158

文献信息

• Divergence of Biochemical Function in the HAD Superfamily: <scp>d</scp>-<i>glycero</i>-<scp>d</scp><i>-manno-</i>Heptose-1,7-bisphosphate Phosphatase (GmhB)
  作者：Liangbing Wang、Hua Huang、Henry H. Nguyen、Karen N. Allen、Patrick S. Mariano、Debra Dunaway-Mariano

  DOI：10.1021/bi902018y

  日期：2010.2.16

  D-glycero-D-manno-Heptose-1,7-bisphosphate phosphatase (GmhB) is a member of the histidinol-phosphate phosphatase (HisB) subfamily of the haloalkanoic acid dehalogenase (HAD) enzyme superfamily. GmhB supports two divergent biochemical pathways in bacteria: the D-glycero-D-manno-heptose-1 alpha-GDP pathway (in S-layer glycoprotein biosynthesis) and the L-glycero-D-manno-heptose-1 beta-ADP pathway (in lipid A biosynthesis). Herein, we report the comparative analysis Of Substrate recognition in selected GmhB orthologs. The substrate specificity of the L-glycero-D-manno-heptose-1 beta-ADP pathway GmhB from Escherichia coli K-12 was evaluated using hexose and heptose bisphosphates, histidinol phosphate, and common organophosphate metabolites. Only D-glycero-D-manno-heptose 1 beta,7-bisphosphate (k(cat)/k(m) = 7 x 10(6) M-1 s(-1)) and D-glycero-D-manno-heptose 1 alpha,7-bisphosphate (k(cat)/K-m, = 7 x 10(4) M-1 s(-1)) displayed physiologically significant Substrate activity. P-31 NMR analysis demonstrated that E. coli GmhB selectively removes the C(7) phosphate. Steady-state kinetic inhibition studies showed that D-glycero-D-manno-heptose 1 beta-phosphate (K-is = 60 mu M, and K-ii = 150 mu M) and histidinol phosphate (K-is = 1 mM, and K-ii = 6 mM), while not hydrolyzed, do in fact bind to E. coli GmhB, which leads to the conclusion that nonproductive binding contributes to substrate discrimination. High catalytic efficiency and a narrow substrate range are characteristic of a well-evolved metabolic enzyme, and as such, E. coli GmhB is set apart from most HAD phosphatases (which are typically inefficient and promiscuous). The specialization of the biochemical function of GmhB was examined by measuring the kinetic constants for hydrolysis of the alpha- and beta-anomers of D-glycero-D-manno-heptose 1 beta,7-bisphosphate catalyzed by the GmhB orthologs of the L-glycero-D-manno- 1 beta-ADP pathways operative in Bordetella bronchiseptica and Mesorhizobium and by the GmhB of the D-glycero-D-manno-heptose 1 alpha-GDP pathway operative in Bacteroides thetaiotaomicron. The results show that although each of these representatives possesses physiologically significant catalytic activity toward both anomers, each displays substantial anomeric specificity. Like E. coli GmhB, B. bronchiseptica GmhB and M. loti GmhB prefer the beta-anomer, whereas B. thetaiotaomicron GmhB is selective for the alpha-anomer. By determining the anomeric configuration of the physiological Substrate (D-glycero-D-manno-heptose 1,7- for each of the four GmhB orthologs, we discovered that the anomeric specificity of GmhB correlates with that of the pathway kinase. The conclusion drawn from this finding is that the evolution of the ancestor to GmhB in the HisB subfamily provided for specialization toward two distinct biochemical functions.
• Chemical Synthesis of <scp>d</scp>-<i>glycero</i>-<scp>d</scp>-<i>manno</i>-Heptose 1,7-Bisphosphate and Evaluation of Its Ability to Modulate NF-κB Activation
  作者：Shinsuke Inuki、Toshihiko Aiba、Shota Kawakami、Taishin Akiyama、Jun-ichiro Inoue、Yukari Fujimoto

  DOI：10.1021/acs.orglett.7b01158

  日期：2017.6.16

  and glycolipids. HBP β-anomer was recently reported to be a pathogen-associated molecular pattern (PAMP) that regulates TIFA-dependent immunity. Herein, we report the chemical synthesis of HBP α- and β-anomers, which highlights a C-7 carbon homologation via the Corey–Chaykovsky reaction, and the introduction of a phosphate group at the anomeric position using the Mitsunobu reaction. Furthermore, NF-κB

  d -甘油基- d -甘露-Heptose 1,7-二磷酸（HBP）是庚糖残基的前体在革兰氏阴性细菌膜表面糖蛋白和糖脂中。最近报道，HBPβ-异头物是一种病原体相关分子模式（PAMP），可调节TIFA依赖性免疫。在这里，我们报道了HBPα-和β-端基异构体的化学合成，该反应突出了通过Corey-Chaykovsky反应的C-7碳同系物，以及使用Mitsunobu反应在端基异构体位置引入了磷酸基团。此外，NF-κB报告基因检测表明，HBPβ-异头物激活了NF-κB信号传导途径。
• Structural Determinants of Substrate Recognition in the HAD Superfamily Member <scp>d</scp>-<i>glycero</i>-<scp>d</scp>-<i>manno</i>-Heptose-1,7-bisphosphate Phosphatase (GmhB),
  作者：Henry H. Nguyen、Liangbing Wang、Hua Huang、Ezra Peisach、Debra Dunaway-Mariano、Karen N. Allen

  DOI：10.1021/bi902019q

  日期：2010.2.16

  The haloalkanoic acid dehalogenase (HAD) enzyme superfamily is the largest family of phosphohydrolases. In HAD members, the structural elements that provide the binding interactions that support substrate specificity are separated from those that orchestrate catalysis. For most HAD phosphatases, a cap domain functions in substrate recognition. However, for the HAD phosphatases that lack a cap domain, an alternate strategy for substrate selection must be operative. One such HAD phosphatase, GmhB of the HisB Subfamily, was selected for structure-function. analysis. Herein, the X-ray crystallographic structures of Escherichia coli GmhB in the apo form (1.6 angstrom resolution), in a complex with Mg2+ and orthophosphate (1.8 angstrom resolution), and in a complex with Mg2+ and D-glycero-D-manno-heptose 1 beta,7-bisphosphate (2.2 angstrom resolution) were determined, in addition to the Structure of Bordetella bronchiseptica GmhB bound to Mg2+ and orthophosphate (1.7 angstrom resolution). The Structures show that in place of a cap domain, the GmhB catalytic site is elaborated by three peptide inserts or loops that pack to form a concave, semicircular surface around the substrate leaving group. Structure-guided kinetic analysis of site-directed mutants was conducted in parallel with a bioinformatics study of sequence diversification within (lie HisB subfamily to identify loop residues that serve as substrate recognition elements and that distinguish GmhB from its subfamily counterpart, the histidinol-phosphate phosphatase domain of HisB. We show that GmhB and the histidinol-phosphate phosphatase domain use the same design of three Substrate recognition loops inserted into the cap domain yet, through selective residue usage on the loops, have achieved unique substrate specificity and thus novel biochemical function.