2-羟基-6-氧代-6-苯基己-2,4-二烯酸 | 54797-48-7

• 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
• 中文名称: 2-羟基-6-氧代-6-苯基己-2,4-二烯酸
• 英文名称: 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid
• 英文别名: HOPDA；HPDA；2-Hydroxy-6-oxo-6-phenyl-hexa-2,4-diensaeure
• CAS: 54797-48-7；50480-67-6
• 化学式: C₁₂H₁₀O₄
• 分子量: 218.209
• InChiKey: RDRDHXDYMGUCKE-UHFFFAOYSA-N

物化性质

• LogP：
  1.189 (est)

计算性质

• 辛醇/水分配系数(LogP)：
  1.95
• 重原子数：
  16.0
• 可旋转键数：
  4.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  74.6
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  2-羟基-6-氧代-6-苯基己-2,4-二烯酸 反应 0.33h， 生成
  参考文献：
  名称：

  ameta 裂解产物水解酶中酰基酶中间体的鉴定揭示了催化三联体的多功能性

  摘要：

  元裂解产物 (MCP) 水解酶是 α/β-水解酶超家族的成员，它利用 Ser-His-Asp 三联体催化 CC 键的水解。BphD，来自联苯降解途径的 MCP 水解酶，将 2-羟基-6-氧代-6-苯基六-2,4-二烯酸 (HOPDA) 水解为 2-羟基五-2,4-二烯酸 (HPD) 和苯甲酸酯。与 HOPDA 孵育的 BphD H265Q 的 1.6 Å 分辨率晶体结构显示该酶的催化丝氨酸被苯甲酰化。酰基酶通过来自“氧阴离子孔”残基的酰胺主链的氢键稳定，这与 Ser112 亲核攻击期间形成的四面体氧阴离子一致。化学淬灭和质谱研究证实了野生型 BphD 中 Ser112-苯甲酰基物质的形成和衰变，其时间尺度与转换和将单当量 (18)O 掺入到 H(2) 水解过程中产生的苯甲酸盐中一致)(18)O。快速扫描动力学研究表明，催化组氨酸对酰化速率的贡献仅一个数量级，但对脱酰化速率的影响超过 5 个

  DOI：

  10.1021/ja208544g
• 作为产物：
  描述：

  2,3-二羟基联苯 在 2'-aminobiphenyl-2,3-diol 1,2-dioxygenase 、 Tris*HCl buffer 作用下， 生成 2-羟基-6-氧代-6-苯基己-2,4-二烯酸
  参考文献：
  名称：

  Purification and Characterization ofmeta-Cleavage Compound Hydrolase from a Carbazole DegraderPseudomonas resinovoransStrain CA10

  摘要：

  2-羟基-6-氧代-6-(2'-氨基苯基)-六-2,4-二烯酸[6-(2'-氨基苯基)-HODA]水解酶参与食树脂假单胞菌菌株 CA10 的咔唑降解，从过度表达的大肠杆菌菌株中纯化至接近同质。该酶为二聚体，其最适pH为7.0-7.5。系统发育分析表明该酶与参与单环芳香族化合物降解的其他水解酶有密切关系，并且该酶对2-羟基-6-氧代-6-苯基六-2,4-二烯酸（6-苯基- HODA)，对 2-羟基-6-氧七-2,4-二烯酸和 2-羟基粘康半醛几乎没有活性。对于 6-苯基-HODA（50 mM 磷酸钠，pH 7.5，25°C），该酶的 Km 为 2.51 μM，kcat 为 2.14 (s−1)。发现6-苯基-HODA的苯基部分2'位上的氨基或羟基的存在对酶活性的影响很小；活性降低的顺序为：6-(2'-氨基苯基)-HODA (2.44 U/mg)>6-苯基-HODA (1.99 U/mg)>2-羟基-6-氧代-6-(2' -羟基苯基）-六-2,4-二烯酸（1.05 U/mg）。 2'-取代对活性的影响与基于计算的这些底物的最低未占据分子轨道能量所预测的反应性一致。

  DOI：

  10.1271/bbb.67.36

文献信息

• Catalytic Promiscuity of Ancestral Esterases and Hydroxynitrile Lyases
  作者：Titu Devamani、Alissa M. Rauwerdink、Mark Lunzer、Bryan J. Jones、Joanna L. Mooney、Maxilmilien Alaric O. Tan、Zhi-Jun Zhang、Jian-He Xu、Antony M. Dean、Romas J. Kazlauskas

  DOI：10.1021/jacs.5b12209

  日期：2016.1.27

  esterase substrates and six lyase substrates found higher catalytic promiscuity among the ancestral enzymes (P < 0.01). Ancestral esterases were more likely to catalyze a lyase reaction than modern esterases, and the ancestral HNL was more likely to catalyze ester hydrolysis than modern HNL's. One ancestral enzyme (HNL1) along the path from esterase to hydroxynitrile lyases was especially promiscuous

  催化混杂是一种有用但偶然的酶特性，因此在自然界中寻找催化混杂酶的效率很低。一些祖先的酶是新酶进化的分支点，并且被假设是混杂的。为了检验祖先酶比其现代后代更混杂的假设，我们在约 1 亿年前的酯酶分歧的羟基腈裂合酶 (HNL) 的四个分支点重建了祖先酶。两种酶类型都是α/β-水解酶折叠酶，具有相同的催化三联体，但反应类型和机制不同。酯酶通过酰基酶中间体催化水解，而裂合酶则在没有中间体的情况下催化消除。用六种酯酶底物和六种裂合酶底物筛选祖先酶及其现代后代，发现祖先酶之间具有更高的催化混杂性（P < 0.01）。祖先的酯酶比现代的酯酶更有可能催化裂合酶反应，并且祖先的HNL比现代的HNL更有可能催化酯水解。从酯酶到羟基腈裂合酶的路径中的一种祖先酶（HNL1）特别混杂，并且催化许多底物的水解和裂合酶反应。更广泛的筛选测试了未通过进化选择的机械相关反应：脱羧、迈克尔加成、γ-内酰胺水解和 1,5-二酮
• The Catalytic Serine of <i>meta</i>-Cleavage Product Hydrolases Is Activated Differently for C–O Bond Cleavage Than for C–C Bond Cleavage
  作者：Antonio C. Ruzzini、Geoff P. Horsman、Lindsay D. Eltis

  DOI：10.1021/bi300663r

  日期：2012.7.24

  triad to catalyze hydrolysis via an acyl–enzyme intermediate. BphD, which catalyzes the hydrolysis of 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid (HOPDA) in biphenyl degradation, catalyzed the hydrolysis of an ester analogue, p-nitrophenyl benzoate (pNPB), with a kcat value (6.3 ± 0.5 s–1) similar to that of HOPDA (6.5 ± 0.5 s–1). Consistent with the breakdown of a shared intermediate, product analyses

  间位裂解产物（MCP）水解酶催化细菌对芳香族化合物的有氧分解代谢中的C–C键裂变。这些酶利用Ser-His-Asp三联体通过酰基酶中间体催化水解。BphD在联苯降解中催化2-羟基-6-氧代-6-苯基六-2,4-二烯酸（HOPDA）的水解，并催化酯类似物对硝基苯甲酸苯酯（pNPB）的水解。k cat值（6.3±0.5 s –1）与HOPDA（6.5±0.5 s –1）相似）。与共有中间体的分解一致，产物分析表明，BphD催化HOPDA和pNPB的甲醇分解，将产物以相似的比例分配给苯甲酸和苯甲酸甲酯。在短的伯醇（甲醇>乙醇>正丙醇）存在下，HOPDA的周转速度提高了4倍，这表明在催化过程中脱酰作用是限速的。在HOPDA的稳态水解中，k cat / K m值与甲醇浓度无关，而k cat和K m值随甲醇浓度增加。该结果与亲核催化的简单模型一致。尽管在甲醇浓度> 250 mM时无法用pNPB饱和该酶，但k
• Purification and Characterization of<i>meta</i>-Cleavage Compound Hydrolase from a Carbazole Degrader<i>Pseudomonas resinovorans</i>Strain CA10
  作者：Hideaki NOJIRI、Hiroko TAIRA、Kenichi IWATA、Kenichi MORII、Jeong-Won NAM、Takako YOSHIDA、Hiroshi HABE、Shugo NAKAMURA、Kentaro SHIMIZU、Hisakazu YAMANE、Toshio OMORI

  DOI：10.1271/bbb.67.36

  日期：2003.1

  2-Hydroxy-6-oxo-6-(2′-aminophenyl)-hexa-2,4- dienoic acid [6-(2′-aminophenyl)-HODA] hydrolase, involved in carbazole degradation by Pseudomonas resinovorans strain CA10, was purified to near homogeneity from an overexpressing Escherichia coli strain. The enzyme was dimeric, and its optimum pH was 7.0-7.5. Phylogenetic analysis showed the close relationship of this enzyme to other hydrolases involved in the degradation of monocyclic aromatic compounds, and this enzyme was specific for 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid (6-phenyl-HODA), having little activity toward 2-hydroxy-6-oxohepta-2,4-dienoic acid and 2-hydroxymuconic semialdehyde. The enzyme had a Km of 2.51 μM and kcat of 2.14 (s−1) for 6-phenyl-HODA (50 mM sodium phosphate, pH 7.5, 25°C). The effect of the presence of an amino group or hydroxyl group at the 2′-position of phenyl moiety of 6-phenyl-HODA on the enzyme activity was found to be small; the activity decreased only in the order of 6-(2′-aminophenyl)-HODA (2.44 U/mg)>6-phenyl-HODA (1.99 U/mg)>2-hydroxy-6-oxo-6-(2′-hydroxyphenyl)-hexa-2,4-dienoic acid (1.05 U/mg). The effects of 2′-substitution on the activity were in accordance with the predicted reactivity based on the calculated lowest unoccupied molecular orbital energy for these substrates.

  2-羟基-6-氧代-6-(2'-氨基苯基)-六-2,4-二烯酸[6-(2'-氨基苯基)-HODA]水解酶参与食树脂假单胞菌菌株 CA10 的咔唑降解，从过度表达的大肠杆菌菌株中纯化至接近同质。该酶为二聚体，其最适pH为7.0-7.5。系统发育分析表明该酶与参与单环芳香族化合物降解的其他水解酶有密切关系，并且该酶对2-羟基-6-氧代-6-苯基六-2,4-二烯酸（6-苯基- HODA)，对 2-羟基-6-氧七-2,4-二烯酸和 2-羟基粘康半醛几乎没有活性。对于 6-苯基-HODA（50 mM 磷酸钠，pH 7.5，25°C），该酶的 Km 为 2.51 μM，kcat 为 2.14 (s−1)。发现6-苯基-HODA的苯基部分2'位上的氨基或羟基的存在对酶活性的影响很小；活性降低的顺序为：6-(2'-氨基苯基)-HODA (2.44 U/mg)>6-苯基-HODA (1.99 U/mg)>2-羟基-6-氧代-6-(2' -羟基苯基）-六-2,4-二烯酸（1.05 U/mg）。 2'-取代对活性的影响与基于计算的这些底物的最低未占据分子轨道能量所预测的反应性一致。
• Characterization of a Transcriptional Regulatory Gene Involved in Dibenzofuran Degradation by<i>Nocardioides</i>sp. Strain DF412
  作者：Parichat SUKDA、Nao GOUDA、Emi ITO、Keisuke MIYAUCHI、Eiji MASAI、Masao FUKUDA

  DOI：10.1271/bbb.80496

  日期：2009.3.23

  Nocardioides sp. DF412 degrades dibenzofuran (DF) to salicylate through the sequential actions of DF dioxygenase (dfdA), extradiol dioxygenase (dfdB), and hydrolase (dfdC). The involvement of a TetR-type regulator gene dfdS in the dfdB and dfdS gene expression was investigated. A reporter assay using a luciferase gene indicated repression of dfdB and dfdS promoter activities in the presence of the dfdS gene product, DfdS. Gel shift analysis indicated specific binding of DfdS to the dfdB promoter region. Both the presence of a DF-degradation intermediate, 2,2′,3-trihydroxybiphenyl (2,2′,3-THBP) or its analog, 2,3-dihydroxybiphenyl (2,3-DHBP), and mutation in the inverted repeat (IR) in the dfdB promoter, canceled repression by DfdS in vivo and the binding of DfdS to the dfdB promoter fragment in vitro. These results suggest derepression of DfdS in the presence of 2,2′,3-THBP and 2,3-DHBP and the involvement of the IR in the repression by DfdS.

  Nocardioides sp. DF412通过DF二氧酶（dfdA）、二醇外二氧酶（dfdB）和水解酶（dfdC）的连续作用将二苯并呋喃（DF）降解为水杨酸盐。研究人员对 TetR 型调节基因 dfdS 参与 dfdB 和 dfdS 基因表达的情况进行了调查。使用荧光素酶基因进行的报告分析表明，在 dfdS 基因产物 DfdS 的存在下，dfdB 和 dfdS 启动子的活性受到抑制。凝胶转移分析表明 DfdS 与 dfdB 启动子区域有特异性结合。DF 降解中间体 2,2′,3-三羟基联苯（2,2′,3-THBP）或其类似物 2,3-二羟基联苯（2,3-DHBP）的存在，以及 dfdB 启动子中倒置重复（IR）的突变，都取消了 DfdS 在体内的抑制作用，也取消了 DfdS 在体外与 dfdB 启动子片段的结合。这些结果表明，在 2,2′,3-THBP和 2,3-DHBP存在的情况下，DfdS的抑制作用减弱，IR参与了DfdS的抑制作用。
• Characterization of a Carbon-Carbon Hydrolase from Mycobacterium tuberculosis Involved in Cholesterol Metabolism
  作者：Nathan A. Lack、Katherine C. Yam、Edward D. Lowe、Geoff P. Horsman、Robin L. Owen、Edith Sim、Lindsay D. Eltis

  DOI：10.1074/jbc.m109.058081

  日期：2010.1

  In the recently identified cholesterol catabolic pathway of Mycobacterium tuberculosis, 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoate hydrolase (HsaD) is proposed to catalyze the hydrolysis of a carbon-carbon bond in 4,5-9,10-diseco-3-hydroxy-5,9,17-tri-oxoandrosta-1(10),2-diene-4-oic acid (DSHA), the cholesterol meta-cleavage product (MCP) and has been implicated in the intracellular survival of the pathogen. Herein, purified HsaD demonstrated 4-33 times higher specificity for DSHA (k(cat)/K(m) = 3.3 +/- 0.3 x 10(4) m(-1) s(-1)) than for the biphenyl MCP 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid (HOPDA) and the synthetic analogue 8-(2-chlorophenyl)-2-hydroxy-5-methyl-6-oxoocta-2,4-dienoic acid (HOPODA), respectively. The S114A variant of HsaD, in which the active site serine was substituted with alanine, was catalytically impaired and bound DSHA with a K(d) of 51 +/- 2 mum. The S114A.DSHA species absorbed maximally at 456 nm, 60 nm red-shifted versus the DSHA enolate. Crystal structures of the variant in complex with HOPDA, HOPODA, or DSHA to 1.8-1.9 Aindicate that this shift is due to the enzyme-induced strain of the enolate. These data indicate that the catalytic serine catalyzes tautomerization. A second role for this residue is suggested by a solvent molecule whose position in all structures is consistent with its activation by the serine for the nucleophilic attack of the substrate. Finally, the alpha-helical lid covering the active site displayed a ligand-dependent conformational change involving differences in side chain carbon positions of up to 6.7 A, supporting a two-conformation enzymatic mechanism. Overall, these results provide novel insights into the determinants of specificity in a mycobacterial cholesterol-degrading enzyme as well as into the mechanism of MCP hydrolases.