4-hydroxy-2-oxo-1,7-heptane-dioate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: 4-hydroxy-2-oxo-1,7-heptane-dioate
• 英文别名: 4-Hydroxy-2-oxoheptanedioate
• 化学式: C₇H₈O₆
• 分子量: 188.137
• InChiKey: HNOAJOYERZTSNK-UHFFFAOYSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  118
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-hydroxy-2-oxo-1,7-heptane-dioate 在 盐酸 作用下， 生成 3-(4,5-dioxooxolan-2-yl)propanoic acid
  参考文献：
  名称：

  Comparison of Two Metal-Dependent Pyruvate Aldolases Related by Convergent Evolution: Substrate Specificity, Kinetic Mechanism, and Substrate Channeling

  摘要：

  HpaI and BphI are two pyruvate class II aldolases found in aromatic meta-cleavage degradation pathways that catalyze similar reactions but are not related in sequence. Steady-state kinetic analysis of the aldol addition reactions and product inhibition assays showed that HpaI exhibits a rapid equilibrium random order mechanism while BphI exhibits a compulsory order mechanism, with pyruvate binding first. Both aldolases are able to utilize aldehyde acceptors two to five carbons in length; however, HpaI showed broader specificity and had a preference for aldehydes containing longer linear alkyl chains or C2-OH substitutions. Both enzymes were able to bind 2-keto acids larger than pyruvate, but only HpaI was able to utilize both pyruvate and 2-ketobutanoate as carbonyl donors in the aldol addition reaction. HpaI lacks stereospecific control producing racemic mixtures of 4-hydroxy-2-oxopentanoate (HOPA) from pyruvate and acetaldehyde while BphI synthesizes only (4S)-HOPA. BphI is also able to utilize acetaldehyde produced by the reduction of acetyl-CoA catalyzed by the associated aldehyde dehydrogenase, BphJ. This aldehyde was directly channeled from the dehydrogenase to the aldolase active sites, with an efficiency of 84%. Furthermore, the BphJ reductive deacylation reaction increased 4-fold when BphI was catalyzing the aldol addition reaction. Therefore, the BphI-BphJ enzyme complex exhibits unique bidirectionality in substrate channeling and allosteric activation.

  DOI：

  10.1021/bi100251u
• 作为产物：
  描述：

  琥珀半醛 、 sodium pyruvate 在 pyruvate aldolase HpaI 、 cobalt(II) chloride 作用下， 反应 0.17h， 生成 4-hydroxy-2-oxo-1,7-heptane-dioate
  参考文献：
  名称：

  Comparison of Two Metal-Dependent Pyruvate Aldolases Related by Convergent Evolution: Substrate Specificity, Kinetic Mechanism, and Substrate Channeling

  摘要：

  HpaI and BphI are two pyruvate class II aldolases found in aromatic meta-cleavage degradation pathways that catalyze similar reactions but are not related in sequence. Steady-state kinetic analysis of the aldol addition reactions and product inhibition assays showed that HpaI exhibits a rapid equilibrium random order mechanism while BphI exhibits a compulsory order mechanism, with pyruvate binding first. Both aldolases are able to utilize aldehyde acceptors two to five carbons in length; however, HpaI showed broader specificity and had a preference for aldehydes containing longer linear alkyl chains or C2-OH substitutions. Both enzymes were able to bind 2-keto acids larger than pyruvate, but only HpaI was able to utilize both pyruvate and 2-ketobutanoate as carbonyl donors in the aldol addition reaction. HpaI lacks stereospecific control producing racemic mixtures of 4-hydroxy-2-oxopentanoate (HOPA) from pyruvate and acetaldehyde while BphI synthesizes only (4S)-HOPA. BphI is also able to utilize acetaldehyde produced by the reduction of acetyl-CoA catalyzed by the associated aldehyde dehydrogenase, BphJ. This aldehyde was directly channeled from the dehydrogenase to the aldolase active sites, with an efficiency of 84%. Furthermore, the BphJ reductive deacylation reaction increased 4-fold when BphI was catalyzing the aldol addition reaction. Therefore, the BphI-BphJ enzyme complex exhibits unique bidirectionality in substrate channeling and allosteric activation.

  DOI：

  10.1021/bi100251u

文献信息

• Purification and Biochemical Characterization of a Pyruvate-Specific Class II Aldolase, HpaI
  作者：Weijun Wang、Stephen Y. K. Seah

  DOI：10.1021/bi050607y

  日期：2005.7.1

  analogue of the enolate intermediate of the enzyme-catalyzed reaction, is a competitive inhibitor of the enzyme, with a K(i) value of 5.5 microM. Replacement of an active site arginine residue (R70) with alanine by site-specific mutagenesis resulted in an enzyme that lacks both aldolase and decarboxylase activities. The mutant enzyme is also unable to catalyze pyruvate proton exchange. The dissociation

  HpaI，II类丙酮酸特异性醛缩酶，与羟苯乙酸的分解代谢途径有关，被过表达和纯化。基于HpaI的生化研究并未证实基于同源2-dehydro-3-deoxygalactarate醛缩酶的晶体结构，磷酸盐参与丙酮酸的质子转移。因此，在HEPES钠缓冲液和Tris-乙酸盐缓冲液中，酶对底物4-羟基-2-酮戊酸的比活度高于磷酸钠缓冲液。该酶还催化无丙酮缓冲液中丙酮酸质​​子交换的部分反应，初始速率为0.77 mmol min（-）（1）mg（-）（1），通过核磁共振监测。稳态动力学分析表明，该酶还能够催化4-羟基-2-酮己酸和3-脱氧-d-甘露糖-辛基-2-核糖酸（KDO）的羟醛裂解。该酶显示出明显的草酰乙酸脱羧酶活性，其ak（cat）值比4-羟基-2-酮戊酸的羟醛裂解的相应值高2.4倍。草酸钠是酶催化反应的烯醇中间体的类似物，是该酶的竞争性抑制剂，K（i）值为5.5 microM。通过位点特异性
• Comparison of Two Metal-Dependent Pyruvate Aldolases Related by Convergent Evolution: Substrate Specificity, Kinetic Mechanism, and Substrate Channeling
  作者：Weijun Wang、Perrin Baker、Stephen Y. K. Seah

  DOI：10.1021/bi100251u

  日期：2010.5.4

  HpaI and BphI are two pyruvate class II aldolases found in aromatic meta-cleavage degradation pathways that catalyze similar reactions but are not related in sequence. Steady-state kinetic analysis of the aldol addition reactions and product inhibition assays showed that HpaI exhibits a rapid equilibrium random order mechanism while BphI exhibits a compulsory order mechanism, with pyruvate binding first. Both aldolases are able to utilize aldehyde acceptors two to five carbons in length; however, HpaI showed broader specificity and had a preference for aldehydes containing longer linear alkyl chains or C2-OH substitutions. Both enzymes were able to bind 2-keto acids larger than pyruvate, but only HpaI was able to utilize both pyruvate and 2-ketobutanoate as carbonyl donors in the aldol addition reaction. HpaI lacks stereospecific control producing racemic mixtures of 4-hydroxy-2-oxopentanoate (HOPA) from pyruvate and acetaldehyde while BphI synthesizes only (4S)-HOPA. BphI is also able to utilize acetaldehyde produced by the reduction of acetyl-CoA catalyzed by the associated aldehyde dehydrogenase, BphJ. This aldehyde was directly channeled from the dehydrogenase to the aldolase active sites, with an efficiency of 84%. Furthermore, the BphJ reductive deacylation reaction increased 4-fold when BphI was catalyzing the aldol addition reaction. Therefore, the BphI-BphJ enzyme complex exhibits unique bidirectionality in substrate channeling and allosteric activation.