(1R,3S)-1-isopropyl-3-carboxytetrahydro-β-carboline

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 哈马拉生物碱
• 英文名称: (1R,3S)-1-isopropyl-3-carboxytetrahydro-β-carboline
• 英文别名: (1R,3S)-1-propan-2-yl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-2-ium-3-carboxylate
• 化学式: C₁₅H₁₈N₂O₂
• 分子量: 258.32
• InChiKey: PQJWDNCGZBQHRJ-QWHCGFSZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  65.1
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  异丁醛 、 L-色氨酸 在 硫酸 作用下， 反应 2.0h， 生成 (1S,3S)-1-isopropyl-3-carboxytetrahydro-β-carboline 、 (1R,3S)-1-isopropyl-3-carboxytetrahydro-β-carboline
  参考文献：
  名称：

  Structural Basis for β-Carboline Alkaloid Production by the Microbial Homodimeric Enzyme McbB

  摘要：

  The beta-carboline (beta C) alkaloids occur throughout nature and exhibit diverse biological activities. In contrast to beta C alkaloid synthesis in plants, the biosynthesis in microorganisms remains poorly understood. The recently reported McbB from Marinactinospora thermotolerans is a novel enzyme proposed to catalyze the Pictet-Spengler (PS) reaction of L-tryptophan and oxaloacetaldehyde to produce the beta C scaffold of marinacarbolines. In this study, we solved the crystal structure of McbB complexed with L-tryptophan at 2.48 angstrom resolution, which revealed the novel protein folding of McbB and the totally different structure from those of other PS condensation catalyzing enzymes, such as strictosidine synthase and norcoclaurine synthase from plants. Structural analysis and site-directed mutagenesis confirmed that the previously proposed catalytic Glu97 at the active-site center functions as an acid and base catalyst. Remarkably, the structure-based mutants R72A and H87A, with expanded active-site cavities, newly accepted bulky phenylglyoxal as the aldehyde substrate, to produce 1-benzoyl-3-carboxy-beta-carboline.

  DOI：

  10.1016/j.chembiol.2015.06.006

文献信息

• Structural Basis for β-Carboline Alkaloid Production by the Microbial Homodimeric Enzyme McbB
  作者：Takahiro Mori、Shotaro Hoshino、Shusaku Sahashi、Toshiyuki Wakimoto、Takashi Matsui、Hiroyuki Morita、Ikuro Abe

  DOI：10.1016/j.chembiol.2015.06.006

  日期：2015.7

  The beta-carboline (beta C) alkaloids occur throughout nature and exhibit diverse biological activities. In contrast to beta C alkaloid synthesis in plants, the biosynthesis in microorganisms remains poorly understood. The recently reported McbB from Marinactinospora thermotolerans is a novel enzyme proposed to catalyze the Pictet-Spengler (PS) reaction of L-tryptophan and oxaloacetaldehyde to produce the beta C scaffold of marinacarbolines. In this study, we solved the crystal structure of McbB complexed with L-tryptophan at 2.48 angstrom resolution, which revealed the novel protein folding of McbB and the totally different structure from those of other PS condensation catalyzing enzymes, such as strictosidine synthase and norcoclaurine synthase from plants. Structural analysis and site-directed mutagenesis confirmed that the previously proposed catalytic Glu97 at the active-site center functions as an acid and base catalyst. Remarkably, the structure-based mutants R72A and H87A, with expanded active-site cavities, newly accepted bulky phenylglyoxal as the aldehyde substrate, to produce 1-benzoyl-3-carboxy-beta-carboline.