2-hydroxy-2,4-hexadienedioate

• 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: 2-hydroxy-2,4-hexadienedioate
• 英文别名: 2-hydroxymuconate
• 化学式: C₆H₄O₅
• 分子量: 156.095
• InChiKey: JBEBGTMCZIGUTK-UHFFFAOYSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  -2.52
• 重原子数：
  11.0
• 可旋转键数：
  3.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  100.49
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  2-hydroxy-2,4-hexadienedioate 在 Pseudomonas putida mt-2 4-oxalocrotonate decarboxylase/vinylpyruvate hydratase complex 、 Pseudomonas putida mt-2 4-oxalocrotonate tautomerase 、 双氧水 、 catalase 作用下， 以 aq. phosphate buffer 为溶剂， 反应 1.0h， 以Ca. 7.8 mg的产率得到(S)-3-羟基丁酸
  参考文献：
  名称：

  乙烯基丙酮酸水合酶催化反应的立体化学后果。

  摘要：

  甲立体化学分析已经在两个vinylpyruvate水合酶（VPH），其将2-羟基-2,4-戊二烯酸为2-酮-4-进行小号-hydroxypentanoate在元-fission通路。具有这种途径的细菌菌株可以使用芳香族化合物作为唯一的能源和碳源。使用2-羟基-2,4-戊二烯酸酯的5-甲基和5-氯衍生物以及恶臭假单胞菌mt-2（Pp）和霍乱单胞菌SP-6（Lc）的酶进行分析。在这两种生物中，VPH与该途径中的先前酶（4-草酰巴豆酸脱羧酶（4-OD））形成复合物。在D 2O，氘核被Pp和Lc酶立体定向地掺入产物的C-3和C-5位置。因此，络合物产生（3 S，5 S）-3,5- [di-D] -2-酮-4 S-羟基己酸酯和（3 S，5 R）-3,5- [di-D]- 2-酮基4 R-羟基-5-氯戊酸酯（由于优先顺序的更改，分别为4 R和5 R）。在C-5处的取代（CH 3或Cl）或酶的来源（Pp

  DOI：

  10.1021/acs.biochem.6b00552

文献信息

• Kinetic and Structural Analysis of Two Linkers in the Tautomerase Superfamily: Analysis and Implications
  作者：Bert-Jan Baas、Brenda P. Medellin、Jake A. LeVieux、Kaci Erwin、Emily B. Lancaster、William H. Johnson、Tamer S. Kaoud、R. Yvette Moreno、Marieke de Ruijter、Patricia C. Babbitt、Yan Jessie Zhang、Christian P. Whitman

  DOI：10.1021/acs.biochem.1c00220

  日期：2021.6.8

  The tautomerase superfamily (TSF) is a collection of enzymes and proteins that share a simple β–α–β structural scaffold. Most members are constructed from a single-core β–α–β motif or two consecutively fused β–α–β motifs in which the N-terminal proline (Pro-1) plays a key and unusual role as a catalytic residue. The cumulative evidence suggests that a gene fusion event took place in the evolution of the TSF followed by duplication (of the newly fused gene) to result in the diversification of activity that is seen today. Analysis of the sequence similarity network (SSN) for the TSF identified several linking proteins (“linkers”) whose similarity links subgroups of these contemporary proteins that might hold clues about structure–function relationship changes accompanying the emergence of new activities. A previously uncharacterized pair of linkers (designated N1 and N2) was identified in the SSN that connected the 4-oxalocrotonate tautomerase (4-OT) and cis-3-chloroacrylic acid dehalogenase (cis-CaaD) subgroups. N1, in the cis-CaaD subgroup, has the full complement of active site residues for cis-CaaD activity, whereas N2, in the 4-OT subgroup, lacks a key arginine (Arg-39) for canonical 4-OT activity. Kinetic characterization and nuclear magnetic resonance analysis show that N1 has activities observed for other characterized members of the cis-CaaD subgroup with varying degrees of efficiencies. N2 is a modest 4-OT but shows enhanced hydratase activity using allene and acetylene compounds, which might be due to the presence of Arg-8 along with Arg-11. Crystallographic analysis provides a structural context for these observations.

  双烯酮异构酶超家族（TSF）是一组共享简单β–α–β结构支架的酶和蛋白质。大多数成员由单个核心β–α–β基序或两个连续融合的β–α–β基序构成，其中N-末端脯氨酸（Pro-1）作为催化残基发挥关键而独特的作用。累计证据表明，在TSF的进化过程中发生了基因融合事件，随后对新融合基因进行了复制，从而导致了今天所见的活性多样化。对TSF的序列相似性网络（SSN）分析识别出几种连接蛋白（“连接器”），它们的相似性将这些当代蛋白质的子群联系起来，这可能为新活性出现时伴随的结构–功能关系变化提供线索。在SSN中识别出一对先前未表征的连接器（指定为N1和N2），它们连接了4-草酰基氯烯烃异构酶（4-OT）和顺式-3-氯丙烯酸脱卤酶（cis-CaaD）子群。N1位于cis-CaaD子群中，具有顺式-CaaD活性所需的全面活性位点残基，而N2位于4-OT子群中，缺少用于典型4-OT活性的重要精氨酸（Arg-39）。动力学表征和核磁共振分析显示，N1的活性与cis-CaaD子群中的其他已表征成员相似，且效率各不相同。N2是一个适度的4-OT，但在使用炔烃和乙炔化合物时显示出增强的水合酶活性，这可能与Arg-8和Arg-11的存在有关。晶体学分析为这些观察提供了结构背景。
• Kinetic and Structural Characterization of a Heterohexamer 4-Oxalocrotonate Tautomerase from <i>Chloroflexus aurantiacus</i> J-10-fl: Implications for Functional and Structural Diversity in the Tautomerase Superfamily,
  作者：Elizabeth A. Burks、Christopher D. Fleming、Andrew D. Mesecar、Christian P. Whitman、Scott D. Pegan

  DOI：10.1021/bi100502z

  日期：2010.6.22

  4-Oxalocrotonate tautomerase (4-OT) isozymes play prominent roles in the bacterial utilization of aromatic hydrocarbons as sole carbon sources. These enzymes catalyze the conversion of 2-hydroxy-2,4-hexadienedioate (or 2-hydroxymuconate) to 2-oxo-3-hexenedioate, where Pro-1 functions as a general base and shuttles a proton from the 2-hydroxyl group of the substrate to the C-5 position of the product

  4-草酰巴豆酸互变异构酶 (4-OT) 同工酶在芳香烃作为唯一碳源的细菌利用中发挥着重要作用。这些酶催化 2-羟基-2,4-己二烯二酸酯（或 2-羟基粘康酸）向 2-氧代-3-己烯二酸酯的转化，其中 Pro-1 作为一般碱基，从基板到产品的 C-5 位置。4-OT，来自恶臭假单胞菌的同六聚体mt-2，是研究最广泛的 4-OT 同工酶，也是互变异构酶超家族的创始成员。对五个嗜热细菌基因组的搜索确定了每个基因组中的编码氨基酸序列，该序列已被注释为类似互变异构酶的蛋白质，但缺乏 Pro-1。然而，附近的序列有 Pro-1，但该序列没有被注释为类似互变异构酶的蛋白质。为了表征这组蛋白质，克隆了来自Chloroflexus aurantiacus J-10-fl 的两个基因，并表达了相应的蛋白质。动力学、生化和 X 射线结构分析表明，这两种表达的蛋白质形成功能性异六聚体 4-OT (hh4-OT)，由三个
• Kinetic and structural characterization of DmpI from Helicobacter pylori and Archaeoglobus fulgidus, two 4-oxalocrotonate tautomerase family members
  作者：Jeffrey J. Almrud、Rakhi Dasgupta、Robert M. Czerwinski、Andrew D. Kern、Marvin L. Hackert、Christian P. Whitman

  DOI：10.1016/j.bioorg.2010.07.002

  日期：2010.12

  The tautomerase superfamily consists of structurally homologous proteins that are characterized by a beta-alpha-beta fold and a catalytic amino-terminal proline. 4-Oxalocrotonate tautomerase (4-OT) family members have been identified and categorized into five subfamilies on the basis of multiple sequence alignments and the conservation of key catalytic and structural residues. Representative members from two subfamilies have been cloned, expressed, purified, and subjected to kinetic and structural characterization. The crystal structure of DmpI from Helicobacter pylori (HpDmpI), a 4-OT homolog in subfamily 3, has been determined to high resolution (1.8 angstrom and 2.1 angstrom) in two different space groups. HpDmpI is a homohexamer with an active site cavity that includes Pro-1, but lacks the equivalent of Arg-11 and Arg-39 found in 4-OT. Instead, the side chain of Lys-36 replaces that of Arg-11 in a manner similar to that observed in the trimeric macrophage migration inhibitory factor (MIF), which is the title protein of another family in the superfamily. The electrostatic surface of the active site is also quite different and suggests that HpDmpI might prefer small, monoacid substrates. A kinetic analysis of the enzyme is consistent with the structural analysis, but a biological role for the enzyme remains elusive. The crystal structure of DmpI from Archaeoglobus fulgidus (AfDmpI), a 4-OT homolog in subfamily-4, has been determined to 2.4 angstrom resolution. AfDmpI is also a homohexamer, with a proposed active site cavity that includes Pro-1, but lacks any other residues that are readily identified as catalytic ones related to 4-OT activity. Indeed, the electrostatic potential of the active site differs significantly in that it is mostly neutral, in contrast to the usual electropositive features found in other 4-OT family members, suggesting that AfDmpI might accommodate hydrophobic substrates. A kinetic analysis has been carried out, but does not provide any clues about the type of reaction the enzyme might catalyze. (C) 2010 Elsevier Inc. All rights reserved.
• Stereochemical Consequences of Vinylpyruvate Hydratase-Catalyzed Reactions
  作者：William H. Johnson、Tyler M. M. Stack、Stephanie M. Taylor、Elizabeth A. Burks、Christian P. Whitman

  DOI：10.1021/acs.biochem.6b00552

  日期：2016.7.26

  Cl) or the source of the enzyme (Pp or Lc) does not change the stereochemical outcome. One mechanism that can account for the results is the ketonization of the 5-substituted dienol to the α,β-unsaturated ketone (placing a deuteron at C-5 in D2O), followed by the conjugate addition of water (placing a deuteron at C-3). The stereochemical outcome for VPH (from Pp and Lc) is the same as that reported

  甲立体化学分析已经在两个vinylpyruvate水合酶（VPH），其将2-羟基-2,4-戊二烯酸为2-酮-4-进行小号-hydroxypentanoate在元-fission通路。具有这种途径的细菌菌株可以使用芳香族化合物作为唯一的能源和碳源。使用2-羟基-2,4-戊二烯酸酯的5-甲基和5-氯衍生物以及恶臭假单胞菌mt-2（Pp）和霍乱单胞菌SP-6（Lc）的酶进行分析。在这两种生物中，VPH与该途径中的先前酶（4-草酰巴豆酸脱羧酶（4-OD））形成复合物。在D 2O，氘核被Pp和Lc酶立体定向地掺入产物的C-3和C-5位置。因此，络合物产生（3 S，5 S）-3,5- [di-D] -2-酮-4 S-羟基己酸酯和（3 S，5 R）-3,5- [di-D]- 2-酮基4 R-羟基-5-氯戊酸酯（由于优先顺序的更改，分别为4 R和5 R）。在C-5处的取代（CH 3或Cl）或酶的来源（Pp