trans-Urocanate | 104-98-3

• 物质功能分类: 生物化工 - 氨基酸及其衍生物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: trans-Urocanate
• 英文别名: (E)-3-(1H-imidazol-5-yl)prop-2-enoate
• CAS: 104-98-3
• 化学式: C6H5N2O2-
• 分子量: 137.12
• InChiKey: LOIYMIARKYCTBW-OWOJBTEDSA-M

物化性质

• 熔点：
  226-228 °C(lit.)
• 沸点：
  253.51°C (rough estimate)
• 密度：
  1.3471 (rough estimate)
• 溶解度：
  水中的溶解度为1.5克/升

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  68.8
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT
• WGK Germany：
  3
• RTECS号：
  NI3425200
• 海关编码：
  29332990
• 安全说明：
  S22,S24/25
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

制备方法与用途

生物活性

尿囊酸（Urocanic acid）是皮肤中的主要光线受体，天然以反式尿囊酸的形式存在。

靶点

人类内源性代谢物

体外研究

在表皮的上层，尿囊酸（UCA）形成。这一过程中，filaggrin——一种由profilaggrin经caspase-14切割后生成的富含组氨酸的丝状蛋白，在蛋白酶的作用下分解为氨基酸成分。

反应信息

• 作为产物：
  描述：

  4-imidazolone-5-propanoate 生成 水 、 trans-Urocanate
  参考文献：
  名称：

  Structure and Action of Urocanase

  摘要：

  Urocanase (EC 4.2.1.49) from Pseudomonas putida was crystallized after removing one of the seven free thiol groups. The crystal structure was solved by multiwavelenth anomalous diffraction (MAD) using a selenomethionine derivative and then refined at 1.14 Angstrom resolution. The enzyme is a symmetric homodimer of 2 X 557 amino acid residues with tightly bound NAD(+) cofactors. Each subunit consists of,a typical NAD-binding domain inserted into a larger core domain that forms the dimer interface. The core domain has a novel chain fold and accommodates the substrate urocanate in a surface depression. The NAD domain sits like a lid on the core domain depression and points with the nicotinamide group to the substrate. Substrate, nicotinamide and five water molecules are completely sequestered in a cavity. Most likely, one of these water molecules hydrates the substrate during catalysis. This cavity has to open for substrate passage, which probably means lifting the NAD domain. The observed atomic arrangement at the active center gives rise to a detailed proposal for the catalytic mechanism that is consistent with published chemical data. As expected, the variability of the residues involved is low, as derived from a family of 58 proteins annotated as urocanases in the data banks. However, one well-embedded member of this family showed a significant deviation at the active center indicating an incorrect annotation. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.jmb.2004.07.028

文献信息

• Friedel-Crafts-Type Mechanism for the Enzymatic Elimination of Ammonia from Histidine and Phenylalanine
  作者：László Poppe、János Rétey

  DOI：10.1002/anie.200461377

  日期：2005.6.13

  The surprisingly high catalytic activity and selectivity of enzymes stem from their ability to both accelerate the target reaction and suppress competitive reaction pathways that may even be dominant in the absence of enzymes. For example, histidine and phenylalanine ammonia-lyases (HAL and PAL) trigger the abstraction of the nonacidic beta protons of these amino acids while leaving the much more acidic

  酶出奇的高催化活性和选择性源自它们加速目标反应和抑制竞争性反应途径的能力，这些竞争途径甚至在不存在酶的情况下也可能占主导地位。例如，组氨酸和苯丙氨酸氨裂合酶（HAL和PAL）触发这些氨基酸的非酸性β质子的提取，同时保持更多的酸性铵氢原子不变。两种氨裂解酶都具有催化重要的亲电基团，据信它是脱氢丙氨酸已有30年的历史，但现在通过X射线晶体学和UV光谱法揭示它是高度亲电的5-亚甲基-3,5-二氢咪唑-4-一个（MIO）组。实验表明，该反应是由MIO对底物芳环的亲电攻击引发的。这种不完全的Friedel-Crafts型反应导致β质子的活化及其立体定向抽象，然后消除氨气并再生MIO基团。这种机制的合理性得到了综合模型的支持。还讨论了PAL反应在由丙烯酸芳基酯生物合成对映体纯的α-氨基β-芳基丙酸酯中的应用。
• Characterization of the active site of histidine ammonia-lyase from<i>Pseudomonas putida</i>
  作者：Dagmar Röther、László Poppe、Sandra Viergutz、Birgid Langer、János Rétey

  DOI：10.1046/j.0014-2956.2001.02298.x

  日期：2001.12.1

  Elucidation of the 3D structure of histidine ammonia‐lyase (HAL, EC 4.3.1.3) from Pseudomonas putida by X‐ray crystallography revealed that the electrophilic prosthetic group at the active site is 3,5‐dihydro‐5‐methylidene‐4H‐imidazol‐4‐one (MIO) [Schwede, T.F., Rétey, J., Schulz, G.E. (1999) Biochemistry, 38, 5355–5361]. To evaluate the importance of several amino‐acid residues at the active site for substrate binding and catalysis, we mutated the following amino‐acid codons in the HAL gene: R283, Y53, Y280, E414, Q277, F329, N195 and H83. Kinetic measurements with the overexpressed mutants showed that all mutations resulted in a decrease of catalytic activity. The mutants R283I, R283K and N195A were ≈ 1640, 20 and 1000 times less active, respectively, compared to the single mutant C273A, into which all mutations were introduced. Mutants Y280F, F329A and Q277A exhibited ≈ 55, 100 and 125 times lower activity, respectively. The greatest loss of activity shown was in the HAL mutants Y53F, E414Q, H83L and E414A, the last being more than 20 900‐fold less active than the single mutant C273A, while H83L was 18 000‐fold less active than mutant C273A. We propose that the carboxylate group of E414 plays an important role as a base in catalysis. To investigate a possible participation of active site amino acids in the formation of MIO, we used the chromophore formation upon treatment of HAL with l‐cysteine and dioxygen at pH 10.5 as an indicator. All mutants, except F329A showed the formation of a 338‐nm chromophore arising from a modified MIO group. The UV difference spectra of HAL mutant F329A with the MIO‐free mutant S143A provide evidence for the presence of a MIO group in HAL mutant F329A also. For modelling of the substrate arrangement within the active site and protonation state of MIO, theoretical calculations were performed.
• Structure and Action of Urocanase
  作者：Dirk Kessler、Janos Rétey、Georg E. Schulz

  DOI：10.1016/j.jmb.2004.07.028

  日期：2004.9

  Urocanase (EC 4.2.1.49) from Pseudomonas putida was crystallized after removing one of the seven free thiol groups. The crystal structure was solved by multiwavelenth anomalous diffraction (MAD) using a selenomethionine derivative and then refined at 1.14 Angstrom resolution. The enzyme is a symmetric homodimer of 2 X 557 amino acid residues with tightly bound NAD(+) cofactors. Each subunit consists of,a typical NAD-binding domain inserted into a larger core domain that forms the dimer interface. The core domain has a novel chain fold and accommodates the substrate urocanate in a surface depression. The NAD domain sits like a lid on the core domain depression and points with the nicotinamide group to the substrate. Substrate, nicotinamide and five water molecules are completely sequestered in a cavity. Most likely, one of these water molecules hydrates the substrate during catalysis. This cavity has to open for substrate passage, which probably means lifting the NAD domain. The observed atomic arrangement at the active center gives rise to a detailed proposal for the catalytic mechanism that is consistent with published chemical data. As expected, the variability of the residues involved is low, as derived from a family of 58 proteins annotated as urocanases in the data banks. However, one well-embedded member of this family showed a significant deviation at the active center indicating an incorrect annotation. (C) 2004 Elsevier Ltd. All rights reserved.