4-hydroxyphenylpyruvate | 622-54-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-hydroxyphenylpyruvate
• 英文别名: HPP；4-HPP；3-(4-Hydroxyphenyl)pyruvate；3-(4-hydroxyphenyl)-2-oxopropanoate
• CAS: 622-54-8
• 化学式: C₉H₇O₄
• 分子量: 179.152
• InChiKey: KKADPXVIOXHVKN-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  77.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-hydroxyphenylpyruvate 在 L-谷氨酸 、 磷酸吡哆醛 作用下， 以 水 为溶剂， 反应 4.0h， 以80%的产率得到L-酪氨酸
  参考文献：
  名称：

  Application of E. Coli aspartate transaminase to amino acid synthesis

  摘要：

  DOI：

  10.1016/s0040-4039(00)96374-3
• 作为产物：
  描述：

  3-Hydroxy-1-(4-hydroxyphenyl)-3-oxoprop-1-en-2-olate 在 macrophage migration inhibitory factor 作用下， 生成 4-hydroxyphenylpyruvate
  参考文献：
  名称：

  Structural and Functional Characterization of a Macrophage Migration Inhibitory Factor Homologue from the Marine Cyanobacterium Prochlorococcus marinus,

  摘要：

  Macrophage migration inhibitory factor (MIF) is a multifunctional mammalian cytokine, which exhibits tautomerase and oxidoreductase activity. MIF homologues with pairwise sequence identities to human MIF ranging from 31% to 41% have been detected in various cyanobacteria. The gene encoding the MIF homologue from the marine cyanobacterium Prochlorococcus marinus strain MIT9313 has been cloned and the corresponding protein (PmMIF) overproduced, purified, and subjected to functional and structural characterization. Kinetic and (1)H NMR spectroscopic studies show that PmMIF tautomerizes phenylenolpyruvate and (p-hydroxyphenyl)enolpyruvate at low levels. The N-terminal proline of PmMIF is critical for these reactions because the P1A mutant has strongly reduced tautomerase activities. PmMIF shows high structural homology with mammalian MIFs as revealed by a crystal structure of PmMIF at 1.63 A resolution. MIF contains a Cys-X-X-Cys motif that mediates oxidoreductase activity, which is lacking from PmMIF. Engineering of the motif into PmMIF did not result in oxidoreductase activity but increased the tautomerase activity 8-fold. The shared tautomerase activities and the conservation of the beta-alpha-beta structural fold and key functional groups suggest that eukaryotic MIFs and cyanobacterial PmMIF are related by divergent evolution from a common ancestor. While several MIF homologues have been identified in eukaryotic parasites, where they are thought to play a role in modulating the host immune response, PmMIF is the first nonparasitic, bacterial MIF-like protein characterized in detail. This work sets the stage for future studies which could address the question whether a MIF-like protein from a free-living bacterium possesses immunostimulatory features similar to those of mammalian MIFs and MIF-like proteins found in parasitic nematodes and protozoa.

  DOI：

  10.1021/bi1008276

文献信息

• A thermodynamic investigation of some reactions involving prephenic acid
  作者：N Kishore、M.J Holden、Y.B Tewari、R.N Goldberg

  DOI：10.1006/jcht.1998.0444

  日期：1999.2

  ΔrHmo = − (74 ± 3) kJ· mol−1for the reference reaction: prephenate2−(aq) + NADox−(aq) + H2O(l) = 4-hydroxyphenylpyruvate−(aq) + NADred2−(aq) + HCO3−(aq) + H+(aq). Both results pertain toT = 298.15 K and ionic strengthI = 0. Benson estimates for the entropies lead to approximate values of the equilibrium constantsK ≈ 1·1026andK ≈ 1· 1012, respectively, for the above two reference reactions.

  已经在 298.15 K 温度下测量了以下酶催化反应的反应热焓：prephenate(aq) = phenylpyruvate(aq) + 二氧化碳(aq), prephenate(aq) + NADox(aq) +H2O(l) = 4-羟基苯基丙酮酸 (aq) + NADred(aq) + 二氧化碳 (aq)。这里，NADox 和 NADredare 分别是 β-烟酰胺腺嘌呤二核苷酸的氧化形式和还原形式。使用分子生物学技术通过表达合适的质粒来制备催化这些各自反应的酶，即预苯甲酸脱水酶和预苯甲酸脱氢酶。量热测量与平衡建模计算一起导致参考反应的标准摩尔焓变 ΔrHmo = − (126 ± 5) kJ·mol−1：prephenate2−(aq) = phenylpyruvate−(aq) + HCO3−(aq) . 相似地，ΔrHmo = − (74 ± 3) kJ·mol−1 参考反应：prephenate2−(aq)
• Intermediate Partitioning Kinetic Isotope Effects for the NIH Shift of 4-Hydroxyphenylpyruvate Dioxygenase and the Hydroxylation Reaction of Hydroxymandelate Synthase Reveal Mechanistic Complexity
  作者：Dhara D. Shah、John A. Conrad、Graham R. Moran

  DOI：10.1021/bi400534q

  日期：2013.9.3

  These substitutions result in altered ratios of products that can be used to calculate kinetic isotope effects (KIE) for the formation of a specific product. For HPPD, secondary normal KIEs indicate that cleavage of the bond in the displacement reaction prior to the shift occurs by a homolytic mechanism. NMR analysis of HG derived from HPPD reacting with enantiomerically pure R-3′-deutero-HPP indicates

  4-羟基苯基丙酮酸双加氧酶（HPPD）和羟基扁桃酸合酶（HMS）是相似的酶，可使用底物4-羟基苯基丙酮酸（HPP）和双氧来催化复杂的双加氧反应。两种酶都将HPP脱羧，然后将所得的羟基苯乙酸（HPA）羟基化。HPPD催化的羟基化反应将HPA的乙酰基取代基以1,2-移位的形式形成2,5-二羟基苯乙酸盐（均相酸盐，HG），而HMS的羟基化反应将羟基置于苄基碳上，形成3'-羟基苯乙酸盐（S-羟基扁桃酸酯，HMA）而无需化学反应。HPPD的野生型形式和两种酶的变体解偶联形成天然和非天然产物。我们已经使用中间分配来探索分叉步骤，这些步骤通过在HPP底物的苄基位置上用氘代替pro来形成这些产物。这些取代导致产物比率的改变，该比率可用于计算特定产物形成的动力学同位素效应（KIE）。对于HPPD，继发的正常KIEs表明，在移位之前，置换反应中的键裂解是通过均溶机理发生的。NMR分析HPPD衍生的HG与对映体
• Structure and Mechanism of the Magnesium-Independent Aromatic Prenyltransferase CloQ from the Clorobiocin Biosynthetic Pathway
  作者：Ute Metzger、Sascha Keller、Clare E.M. Stevenson、Lutz Heide、David M. Lawson

  DOI：10.1016/j.jmb.2010.09.067

  日期：2010.12

  majority of prenyltransferases characterized to date. Our structure of CloQ complexed with 4-hydroxyphenylpyruvate reveals the formation of a covalent link between the substrate and Cys215 to yield a thiohemiketal species. Through site-directed mutagenesis, we show that this link is not essential for enzyme activity in vitro. Furthermore, we demonstrate that CloQ will accept alternative substrates and, therefore

  CloQ​​是一种来自玫瑰色链霉菌变种链霉菌素生物合成途径的芳香异戊二烯基转移酶。oscitans。它涉及抗生素的烯丙基化的羟基苯甲酸酯部分的合成，特别是催化二甲基烯丙基部分与4-羟基苯基丙酮酸酯的连接。在这里，我们报告CloQ的晶体结构，并将其用作解释来自野生型和变异蛋白的生化数据的框架。CloQ​​属于芳香族异戊二烯基转移酶家族，其特征在于其异常的核心折叠包含五个连续的ααββ元素，这些元素形成一个中心10链反平行β-桶。后者描绘了一个可接触溶剂的空腔，在该空腔中底物结合并发生了催化作用。该腔具有明确定义的极性和非极性区域，它们在底物结合中具有独特的作用，并促进了Friedel-Crafts型机理。2+，其中，相比之下，是大多数异戊二烯基转移，其特征在于，以日期的严格要求。我们的CloQ与4-羟苯基丙酮酸盐络合的结构揭示了底物与Cys215之间共价键的形成，从而产生了硫代半缩醛物质。通
• Free energy calculations elucidate substrate binding, gating mechanism, and tolerance‐promoting mutations in herbicide target 4‐hydroxyphenylpyruvate dioxygenase
  作者：Christina E. M. Schindler、Eva Hollenbach、Thomas Mietzner、Klaus‐Jürgen Schleifer、Martin Zacharias

  DOI：10.1002/pro.3612

  日期：2019.6

  4-Hydroxyphenylpyruvate dioxygenase (HPPD) catalyzes the second reaction in the tyrosine catabolism and is linked to the production of cofactors plastoquinone and tocopherol in plants. This important biological role has put HPPD in the focus of current herbicide design efforts including the development of herbicide-tolerant mutants. However, the molecular mechanisms of substrate binding and herbicide

  4-羟基苯基丙酮酸双加氧酶 (HPPD) 催化酪氨酸分解代谢中的第二个反应，并与植物中辅因子质体醌和生育酚的产生有关。这种重要的生物学作用使 HPPD 成为当前除草剂设计工作的焦点，包括开发耐除草剂突变体。然而，底物结合和除草剂耐受性的分子机制尚未阐明。在这项工作中，我们进行了分子动力学模拟和自由能计算，以表征 HPPD 中 C 端螺旋 H11 的活性位点门控。我们比较了拟南芥 (At) 和玉米 (Zm) 野生型蛋白质的门控平衡，从模拟中检索了实验观察到的首选方向。我们研究了底物和产物结合对开闭转变的影响，发现 H11 中配体介导的构象转换可介导快速底物进入，然后通过 H11 打开活性位点关闭和有效产物释放。我们进一步研究了 At 突变体 HPPD 中的 H11 门控，发现与实验测量的除草剂耐受性相关的巨大差异。然后，计算结果被用来设计一种新的 At 突变型 HPPD 蛋白，该蛋白在体外生化实验中显示出对六种市售
• Isolation of Herbicide-Resistant 4-Hydroxyphenylpyruvate Dioxygenase from Cultured<i>Coptis japonica</i>Cells
  作者：Yuling LIANG、Hiromichi MINAMI、Fumihiko SATO

  DOI：10.1271/bbb.80466

  日期：2008.11.23

  4-Hydroxyphenylpyruvate dioxygenase (HPPD) catalyzes the formation of homogentisate from 4-hydroxyphenylpyruvate and O(2). In plants, HPPD has been identified as a molecular target for herbicides. We report the isolation and characterization of a cDNA encoding a HPPD from cultured Coptis japonica cells. Recombinant CjHPPD showed significantly higher half-maximum inhibitory concentration (IC(50)) values

  4-羟基苯基丙酮酸双加氧酶（HPPD）催化从4-羟基苯基丙酮酸和O（2）的尿黑酸盐的形成。在植物中，HPPD已被确定为除草剂的分子靶标。我们报告了从培养的黄连细胞中编码HPPD的cDNA的分离和鉴定。重组CjHPPD显示抑制HPPD的除草剂去甲基吡唑烷基吡唑酸酯的半最大抑制浓度（IC（50））值明显高于其他植物HPPD。