4E-2-hydroxy-2,4-hexadienoate

• 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: 4E-2-hydroxy-2,4-hexadienoate
• 英文别名: Oxypentadienecarboxylic acid；(2Z,4E)-2-hydroxyhexa-2,4-dienoic acid
• 化学式: C₆H₈O₃
• 分子量: 128.128
• InChiKey: VPGPQVKJUYKKNN-IAROGAJJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  9
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  diethyl 5-(methyl)-2-hydroxy-2,4-hexadiene-1,6-dioate 在 sodium hydroxide 作用下， 以 二甲基亚砜 为溶剂， 反应 16.25h， 生成 4E-2-hydroxy-2,4-hexadienoate
  参考文献：
  名称：

  The Contribution of the Substrate's Carboxylate Group to the Mechanism of 4-Oxalocrotonate Tautomerase

  摘要：

  4-Oxalocrotonate tautomerase (4-OT) converts 2-oxo-4E-hexenedioate (1) to 2-oxo-3E-hexenedioate (3) through the dienol intermediate, 2-hydroxy-2,4-hexadiene-1,6-dioate (2). Previous studies established that the isomerization of 1 to 3 is primarily a suprafacial process. It was also suggested that the 6-carboxylate group of the substrate maintains the regio- and stereochemical fidelity of the reaction by anchoring the substrate at the active site. A subsequent study suggested an additional role for the 6-carboxylate group in the mechanism: the enzyme may utilize the binding energy of the carboxylate group to facilitate catalysis. In order to explore the role of the carboxylate group in the mechanism further, the nonenzymatic rate constants for mono- and dicarboxylated substrates were measured and compared to the rates obtained for the corresponding enzymatic reactions. The results show that the missing carboxylate group has a profound effect on enzymatic catalysis as evidenced by the significant decreases (a 10(4)- and a 10(5)-fold reduction) in the values of k(cat)/K-m observed for the two monocarboxylated substrates. A comparison of the nonenzymatic rate constants indicates that the reduced k(cat)/K-m values cannot be explained on the basis of the chemical reactivities. The stereochemical course of the 4-OT-catalyzed reaction was also determined using 2-hydroxy-2,4Z-heptadiene-1,7-dioate. The stereochemical analysis reveals that the presence of the carboxylate group improves the stereoselectivity of the enzyme-catalyzed ketonization of 2-hydroxy-2,4Z-heptadiene-1,7-dioate to 2-oxo-[3-H-2]-4Z-heptene-1,7-dioate in (H2O)-H-2-a result that is consistent with its previously assigned role. These findings provide further evidence that the substrate's carboxylate group contributes to the mechanism of the enzyme in two ways: it anchors the substrate at the active site and it facilitates catalysis by destabilizing the substrate or by stabilizing the transition state. (C) 1998 Academic Press.

  DOI：

  10.1006/bioo.1998.1095

文献信息

• METHODS AND AGENTS FOR TREATING TUBERCULOSIS
  申请人：Eltis Lindsay D.

  公开号：US20100041631A1

  公开（公告）日：2010-02-18

  The present invention relates to the treatment of tuberculosis (mycobacterial infections) by the use of KshAB complex inhibitors, or a KstD molecule, or a HsaAB complex, or a HsaC molecule, or a HsaD molecule. The application also includes a method for identifying an inhibitor or modulator of the previously mentioned molecules and complexes.

  本发明涉及使用KshAB复合物抑制剂、KstD分子、HsaAB复合物、HsaC分子或HsaD分子治疗结核病（分枝杆菌感染）。该申请还包括一种鉴定前述分子和复合物的抑制剂或调节剂的方法。
• [EN] METHODS AND AGENTS FOR TREATING TUBERCULOSIS<br/>[FR] MÉTHODES ET AGENTS DESTINÉS À TRAITER LA TUBERCULOSE
  申请人：UNIV BRITISH COLUMBIA

  公开号：WO2007118329A1

  公开（公告）日：2007-10-25

  [EN] The present invention relates to the treatment of tuberculosis (mycobacterial infections) by the use of KshAB complex inhibitors, or a KstD molecule, or a HsaAB complex, or a HsaC molecule, or a HsaD molecule. The application also includes a method for identifying an inhibitor or modulator of the previously mentioned molecules and complexes.
  [FR] L'invention concerne le traitement de la tuberculose (infections mycobactériennes) à l'aide d'inhibiteurs d'un complexe KshAB, ou d'une molécule KstD, ou d'un complexe HsaAB, ou d'une molécule HsaC, ou d'une molécule HsaD. La présente invention concerne en outre une méthode permettant d'identifier un inhibiteur ou un modulateur des molécules et complexes susmentionnés.