4-methyl-4-hydroxy-2-oxoglutarate | 64215-73-2

• 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-methyl-4-hydroxy-2-oxoglutarate
• 英文别名: 2-hydroxy-2-methyl-4-oxopentanedioate；4-hydroxy-4-methyl-2-oxoglutarate
• CAS: 64215-73-2
• 化学式: C₆H₆O₆
• 分子量: 174.11
• InChiKey: YRWAMSXHYBBHFL-UHFFFAOYSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.5
• 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-methyl-4-hydroxy-2-oxoglutarate 在 Pseudomonas putida F₁ 4-hydroxy-4-methyl-2-oxoglutarate/4-carboxy-4-hydroxy-2-oxoadipate aldolase, molecular mass determined by SDS-PAGE: 26 kDa 、 magnesium chloride 作用下， 生成 piruvate
  参考文献：
  名称：

  Structural and Kinetic Characterization of 4-Hydroxy-4-methyl-2-oxoglutarate/4-Carboxy-4-hydroxy-2-oxoadipate Aldolase, a Protocatechuate Degradation Enzyme Evolutionarily Convergent with the HpaI and DmpG Pyruvate Aldolases

  摘要：

  4-Hydroxy-4-methyl-2-oxoglutarate/4-carboxy-4-hydroxy-2- oxoadipate (HMG/CHA) aldolase from Pseudomonas putida F1 catalyzes the last step of the bacterial protocatechuate 4,5-cleavage pathway. The preferred substrates of the enzyme are 2-keto-4-hydroxy acids with a 4-carboxylate substitution. The enzyme also exhibits oxaloacetate decarboxylation and pyruvate alpha-proton exchange activity. Sodium oxalate is a competitive inhibitor of the aldolase reaction. The pH dependence of k(cat)/K-m and k(cat) for the enzyme is consistent with a single deprotonation with pK(a) values of 8.0 +/- 0.1 and 7.0 +/- 0.1 for free enzyme and enzyme substrate complex, respectively. The 1.8 angstrom x-ray structure shows a four-layered alpha-beta-beta-alpha sandwich structure with the active site at the interface of two adjacent subunits of a hexamer; this fold resembles the RNase E inhibitor, RraA, but is novel for an aldolase. The catalytic site contains a magnesium ion ligated by Asp-124 as well as three water molecules bound by Asp-102 and Glu-199'. A pyruvate molecule binds the magnesium ion through both carboxylate and keto oxygen atoms, completing the octahedral geometry. The carbonyl oxygen also forms hydrogen bonds with the guanadinium group of Arg-123, which site-directed mutagenesis confirms is essential for catalysis. A mechanism for HMG/CHA aldolase is proposed on the basis of the structure, kinetics, and previously established features of other aldolase mechanisms.

  DOI：

  10.1074/jbc.m110.159509
• 作为产物：
  描述：

  piruvate 、 2-(膦酰氧基)丙烯酸酯 在 white potato acid phosphatase 、 magnesium 作用下， 生成 4-methyl-4-hydroxy-2-oxoglutarate
  参考文献：
  名称：

  A new reaction surface for concerted reactions: the metal-ion-catalyzed addition of enolpyruvate to pyruvate

  摘要：

  DOI：

  10.1021/ja00189a028

文献信息

• Structural and Kinetic Characterization of 4-Hydroxy-4-methyl-2-oxoglutarate/4-Carboxy-4-hydroxy-2-oxoadipate Aldolase, a Protocatechuate Degradation Enzyme Evolutionarily Convergent with the HpaI and DmpG Pyruvate Aldolases
  作者：Weijun Wang、Scott Mazurkewich、Matthew S. Kimber、Stephen Y.K. Seah

  DOI：10.1074/jbc.m110.159509

  日期：2010.11

  4-Hydroxy-4-methyl-2-oxoglutarate/4-carboxy-4-hydroxy-2- oxoadipate (HMG/CHA) aldolase from Pseudomonas putida F1 catalyzes the last step of the bacterial protocatechuate 4,5-cleavage pathway. The preferred substrates of the enzyme are 2-keto-4-hydroxy acids with a 4-carboxylate substitution. The enzyme also exhibits oxaloacetate decarboxylation and pyruvate alpha-proton exchange activity. Sodium oxalate is a competitive inhibitor of the aldolase reaction. The pH dependence of k(cat)/K-m and k(cat) for the enzyme is consistent with a single deprotonation with pK(a) values of 8.0 +/- 0.1 and 7.0 +/- 0.1 for free enzyme and enzyme substrate complex, respectively. The 1.8 angstrom x-ray structure shows a four-layered alpha-beta-beta-alpha sandwich structure with the active site at the interface of two adjacent subunits of a hexamer; this fold resembles the RNase E inhibitor, RraA, but is novel for an aldolase. The catalytic site contains a magnesium ion ligated by Asp-124 as well as three water molecules bound by Asp-102 and Glu-199'. A pyruvate molecule binds the magnesium ion through both carboxylate and keto oxygen atoms, completing the octahedral geometry. The carbonyl oxygen also forms hydrogen bonds with the guanadinium group of Arg-123, which site-directed mutagenesis confirms is essential for catalysis. A mechanism for HMG/CHA aldolase is proposed on the basis of the structure, kinetics, and previously established features of other aldolase mechanisms.
• A new reaction surface for concerted reactions: the metal-ion-catalyzed addition of enolpyruvate to pyruvate
  作者：Minsek Cheong、Daniel L. Leussing

  DOI：10.1021/ja00189a028

  日期：1989.3