[4-[[1,3-Dihydroxy-2-(hydroxymethyl)propan-2-yl]iminomethyl]-5-hydroxy-6-methylpyridin-3-yl]methyl dihydrogen phosphate | 114855-98-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: [4-[[1,3-Dihydroxy-2-(hydroxymethyl)propan-2-yl]iminomethyl]-5-hydroxy-6-methylpyridin-3-yl]methyl dihydrogen phosphate
• 英文别名: [4-[[1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl]iminomethyl]-5-hydroxy-6-methylpyridin-3-yl]methyl dihydrogen phosphate
• CAS: 114855-98-0
• 化学式: C₁₂H₁₉N₂O₈P
• 分子量: 350.265
• InChiKey: GKGTZXISICTHPS-UHFFFAOYSA-N

物化性质

• 沸点：
  785.2±70.0 °C(predicted)
• 密度：
  1.59±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.16
• 重原子数：
  23.0
• 可旋转键数：
  8.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  172.93
• 氢给体数：
  6.0
• 氢受体数：
  8.0

反应信息

• 作为产物：
  描述：

  磷酸吡哆醛 、 三羟甲基氨基甲烷 以 水 为溶剂， 生成 [4-[[1,3-Dihydroxy-2-(hydroxymethyl)propan-2-yl]iminomethyl]-5-hydroxy-6-methylpyridin-3-yl]methyl dihydrogen phosphate
  参考文献：
  名称：

  Heme Regulation of Human Cystathionine β-Synthase Activity: Insights from Fluorescence and Raman Spectroscopy

  摘要：

  Cystathionine beta-synthase (CBS) plays a central role in homocysteine metabolism, and malfunction of the enzyme leads to homocystinuria, a devastating metabolic disease. CBS contains a pyridoxal 5'-phosphate (PLP) cofactor which catalyzes the synthesis of cystathionine from homocysteine and serine. Mammalian forms of the enzyme also contain a heme group, which is not involved in catalysis. It may, however, play a regulatory role, since the enzyme is inhibited when CO or NO are bound to the heme. We have investigated the mechanism of this inhibition using fluorescence and resonance Raman spectroscopies. CO binding is found to induce a tautomeric shift of the PLP from the ketoenamine to the enolimine form. The ketoenamine is key to PLP reactivity because its imine C=N bond is protonated, facilitating attack by the nucleophilic substrate, serine. The same tautomer shift is also induced by heat inactivation of Fe(II)CBS, or by an Arg266Met replacement in Fe(II)CBS, which likewise inactivates the enzyme; in both cases the endogenous Cys52 ligand to the heme is replaced by another, unidentified ligand. CO binding also displaces Cys52 from the heme. We propose that the tautomer shift results from loss of a stabilizing H-bond from Asn149 to the PLP ring O3' atom, which is negatively charged in the ketoenamine tautomer. This loss would be induced by displacement of the PLP as a result of breaking the salt bridge between Cys52 and Arg266, which resides on a short helix that is also anchored to the PLP via H-bonds to its phosphate group. The salt bridge would be broken when Cys52 is displaced from the heme. Cys52 protonation is inferred to be the rate-limiting step in breaking the salt bridge, since the rate of the tautomer shift, following CO binding, increases with decreasing pH. In addition, elevation of the concentration of phosphate buffer was found to diminish the rate and extent of the tautomer shift, suggesting a ketoenamine-stabilizing phosphate binding site, possibly at the protonated imine bond of the PLP. Implications of these findings for CBS regulation are discussed.

  DOI：

  10.1021/ja904468w