acetopyruvate | 16709-26-5

• 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: acetopyruvate
• 英文别名: Acetylpyruvate；2,4-dioxopentanoate
• CAS: 16709-26-5
• 化学式: C₅H₅O₄
• 分子量: 129.092
• InChiKey: UNRQTHVKJQUDDF-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  9
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  74.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  acetopyruvate 、 水 生成 乙酸盐 、 氢(+1)阳离子 、 piruvate
  参考文献：
  名称：

  Davey J.F.; Ribbons D.W., J Biol Chem, 1975, 0021-9258, 3826-30

  摘要：

  DOI：
• 作为产物：
  描述：

  2-oxo-3-pentynoate 在 tautomerase superfamily N₁ 作用下， 以 氘代二甲亚砜 、 aq. phosphate buffer 为溶剂， 生成 acetopyruvate
  参考文献：
  名称：

  Kinetic and Structural Analysis of Two Linkers in the Tautomerase Superfamily: Analysis and Implications

  摘要：

  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。

  DOI：

  10.1021/acs.biochem.1c00220

文献信息

• Characterization of a Newly Identified Mycobacterial Tautomerase with Promiscuous Dehalogenase and Hydratase Activities Reveals a Functional Link to a Recently Diverged <i>cis</i>-3-Chloroacrylic Acid Dehalogenase
  作者：Bert-Jan Baas、Ellen Zandvoort、Anna A. Wasiel、Wim J. Quax、Gerrit J. Poelarends

  DOI：10.1021/bi200071k

  日期：2011.4.12

  The enzyme cis-3-chloroacrylic acid dehalogenase (cis-CaaD) is found in a bacterial pathway that degrades a synthetic nematocide, cis-1,3-dichloropropene, introduced in the 20th century. The previously determined crystal structure of cis-CaaD and its promiscuous phenylpyruvate tautomerase (PPT) activity link this dehalogenase to the tautomerase superfamily, a group of homologous proteins that are characterized by a catalytic amino-terminal proline and a beta-alpha-beta structural fold. The low-level PPT activity of cis-CaaD, which may be a vestige of the function of its progenitor, prompted us to search the databases for a homologue of cis-CaaD that was annotated as a putative tautomerase and test both its PPT and cis-CaaD activity. We identified a mycobacterial cis-CaaD homologue (designated MsCCH2) that shares key sequence and active site features with cis-CaaD. Kinetic and H-1 NMR spectroscopic studies show that MsCCH2 functions as an efficient PPT and exhibits low-level promiscuous dehalogenase activity, processing both cis- and trans-3-chloroacrylic acid. To further probe the active site of MsCCH2, the enzyme was incubated with 2-oxo-3-pentynoate (2-OP). At pH 8.5, MsCCH2 is inactivated by 2-OP due to the covalent modification of Pro-1, suggesting that Pro-1 functions as a nucleophile at pH 8.5 and attacks 2-OP in a Michael-type reaction. At pH 6.5, however, MsCCH2 exhibits hydratase activity and converts 2-013 to acetopyruvate, which implies that Pro-1 is cationic at pH 6.5 and not functioning as a nucleophile. At pH 7.5, the hydratase and inactivation reactions occur simultaneously. From these results, it can be inferred that Pro-1 of MsCCH2 has a pK(a) value that lies in between that of a typical tautomerase (pK(a) of Pro-I similar to 6) and that of cis-CaaD (pK(a) of Pro-I similar to 9). The shared activities and structural features, coupled with the intermediate pK(a) of Pro-1, suggest that MsCCH2 could be characteristic of an evolutionary intermediate along the past route for the divergence of cis-CaaD from an unknown superfamily tautomerase. This makes MsCCH2 an ideal candidate for laboratory evolution of its promiscuous dehalogenase activity, which could identify additional features necessary for a fully active cis-CaaD. Such results will provide insight into pathways that could lead to the rapid divergent evolution of an efficient cis-CaaD enzyme.
• 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。
• Davey J.F.; Ribbons D.W., J Biol Chem, 1975, 0021-9258, 3826-30
  作者：Davey J.F.、Ribbons D.W.

  DOI：——

  日期：——