Trimethyl-[2-(octanoylamino)ethyl]azanium | 179617-18-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: Trimethyl-[2-(octanoylamino)ethyl]azanium
• 英文别名: trimethyl-[2-(octanoylamino)ethyl]azanium
• CAS: 179617-18-6
• 化学式: C₁₃H₂₉N₂O
• 分子量: 229.386
• InChiKey: LDXKKFRCWCFRIE-UHFFFAOYSA-O

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  16
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  4,4'-联吡啶二硫醚 、 2-氨基乙基-三甲基铵 、 辅酶 A S-辛酸酯 在 N-terminally His₁₀-tagged human choline acetyltransferase E₃₃₇Y/C₅₅₀A mutant 作用下， 反应 0.5h， 生成 吡啶-4(1H)-硫酮 、 Trimethyl-[2-(octanoylamino)ethyl]azanium
  参考文献：
  名称：

  Redesign of Cosubstrate Specificity and Identification of Important Residues for Substrate Binding to hChAT

  摘要：

  In eukaryotes, choline acetyltransferase (ChAT) catalyzes the reversible formation of the neurotransmitter acetylcholine from choline and acetyl-CoA. ChAT belongs to a family of CoA-dependent enzymes that also includes the carnitine acyltransferases CrAT, CrOT, and CPTs. In contrast to CrOT and CPTs that are very active toward medium-and long-chain acyl-CoAs, respectively, CrAT and ChAT display activity toward only short-chain acyl-CoAs. We recently demonstrated the substrate and cosubstrate promiscuity of the wild-type human ChAT (hChAT). To extend the flexibility of this enzyme, we have generated a series of single, double, and triple hChAT mutants. Here we report the conversion of hChAT into choline octanoyltransferase (ChOT) and choline palmitoyltransferase (ChPT). The E337 and C550 residues (numbering from hChAT) were previously shown to dictate the acyl-CoA cosubstrate specificity in the carnitine series. Here we identify and demonstrate the importance of C551, in addition to E337 and C550, in contributing to the acyl-CoA specificity of hChAT. We also show that either C550 or C551 needs to be present for the transfer of medium-and long-chain acyl-CoAs by hChAT. By exploring the potential expansion of the tunnel on the substrate side, we demonstrate that residues M84, Y436, and Y552 play a critical role in binding and holding the choline substrate in the ChAT active site.

  DOI：

  10.1021/bi1007996

文献信息

• Redesign of Cosubstrate Specificity and Identification of Important Residues for Substrate Binding to hChAT
  作者：Keith D. Green、Vanessa R. Porter、Yaru Zhang、Sylvie Garneau-Tsodikova

  DOI：10.1021/bi1007996

  日期：2010.7.27

  In eukaryotes, choline acetyltransferase (ChAT) catalyzes the reversible formation of the neurotransmitter acetylcholine from choline and acetyl-CoA. ChAT belongs to a family of CoA-dependent enzymes that also includes the carnitine acyltransferases CrAT, CrOT, and CPTs. In contrast to CrOT and CPTs that are very active toward medium-and long-chain acyl-CoAs, respectively, CrAT and ChAT display activity toward only short-chain acyl-CoAs. We recently demonstrated the substrate and cosubstrate promiscuity of the wild-type human ChAT (hChAT). To extend the flexibility of this enzyme, we have generated a series of single, double, and triple hChAT mutants. Here we report the conversion of hChAT into choline octanoyltransferase (ChOT) and choline palmitoyltransferase (ChPT). The E337 and C550 residues (numbering from hChAT) were previously shown to dictate the acyl-CoA cosubstrate specificity in the carnitine series. Here we identify and demonstrate the importance of C551, in addition to E337 and C550, in contributing to the acyl-CoA specificity of hChAT. We also show that either C550 or C551 needs to be present for the transfer of medium-and long-chain acyl-CoAs by hChAT. By exploring the potential expansion of the tunnel on the substrate side, we demonstrate that residues M84, Y436, and Y552 play a critical role in binding and holding the choline substrate in the ChAT active site.