6-Hydroxynicotinate(1-)

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 6-Hydroxynicotinate(1-)
• 英文别名: 6-oxo-1H-pyridine-3-carboxylate
• 化学式: C6H4NO3-
• 分子量: 138.1
• InChiKey: BLHCMGRVFXRYRN-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  69.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-Hydroxynicotinate(1-) 、 水 、 氧气 生成 2,6-Dihydroxynicotinate 、 双氧水
  参考文献：
  名称：

  摘要：

  DOI：
• 作为产物：
  描述：

  铁阳离子 、 水 、 nicotinate 生成 6-Hydroxynicotinate(1-) 、 铁燧石 、 氢(+1)阳离子
  参考文献：
  名称：

  Deciphering the genetic determinants for aerobic nicotinic acid degradation: The nic cluster from Pseudomonas putida KT2440

  摘要：

  烟酸（NA）的有氧分解被认为是降解N-杂环芳香化合物的模型系统之一，其中一些化合物是主要的环境污染物。然而，参与此过程的大多数酶的完整基因组以及结构-功能关系仍然未知。我们已经从Pseudomonas putida KT2440中鉴定了一个基因簇（nic基因），该基因簇负责该细菌中的有氧NA降解，并在异源宿主中表达。通过形成2,5-二羟基吡啶和马来酰基酸的代谢途径已经得到再次审视，一些基因产物成为具有前所未有的分子结构的新型酶的原型。因此，NA的初始羟化由双组分羟化酶（NicAB）催化，该酶是黄嘌呤脱氢酶家族的第一个成员，其电子传递链至分子氧包括细胞色素c结构域。Fe2+依赖性双氧酶（NicX）将2,5-二羟基吡啶转化为N-甲酰马来酰基酸，并成为新型外二元环裂解双氧酶家族的创始成员。进一步将N-甲酰马来酰基酸转化为甲酸和马来酰基酸由NicD蛋白催化，这是迄今为止唯一被描述的去甲酰酶，其催化三联体类似于α / β-酯酶折叠超家族的某些成员。这项工作允许探索腐生菌和一些病原体中是否存在同源基因簇，它们可能刺激对其在致病性中的作用进行研究，并为开发新的生物技术过程以解毒/生物转化N-杂环芳香化合物提供框架。

  DOI：

  10.1073/pnas.0802273105

文献信息

• Nicotinic acid hydroxylase from Clostridium barkeri: electron paramagnetic resonance studies show that selenium is coordinated with molybdenum in the catalytically active selenium-dependent enzyme.
  作者：V N Gladyshev、S V Khangulov、T C Stadtman

  DOI：10.1073/pnas.91.1.232

  日期：1994.1.4

  Nicotinic acid hydroxylase from Clostridium barkeri contains selenium in an unidentified form that is dissociated as a low molecular weight compound upon denaturation of the enzyme. Other cofactors of this enzyme are molybdopterin, FAD, and iron-sulfur clusters. In the current study, we show that the enzyme, as isolated, exhibits a stable Mo(V) electron paramagnetic resonance (EPR) signal ("resting" signal)

  来自巴氏梭状芽胞杆菌的烟酸羟化酶含有一种身份不明的硒，该硒在变性后会作为低分子量化合物解离。该酶的其他辅助因子是钼蝶呤，FAD和铁硫簇。在目前的研究中，我们表明，该酶作为分离物表现出稳定的Mo（V）电子顺磁共振（EPR）信号（“静止”信号），并且该信号与该酶的硒含量和烟酸羟化酶活性相关。酶。正常硒同位素丰度替代77Se会导致天然蛋白质的Mo（V）EPR信号分裂，而不会影响FeS簇的铁信号。从缺乏硒的培养基中生长的细胞中分离出的酶的Mo（V）EPR信号和烟酸羟化酶活性几乎无法检测到。相比之下，FeS簇的EPR信号，电子吸收光谱，NADPH氧化酶活性和色谱行为变化不大，是活性含硒酶的典型特征。还显示了一种EPR信号，该信号表明硒缺乏酶中存在钼。根据这些结果，我们得出结论，可分解的硒部分与钼蝶呤辅因子中的钼直接配位，此外，该硒对于烟酸羟化酶活性至关重要。色谱行为几乎没有变化，这是活性含硒酶的典型
• Properties of the Selenium- and Molybdenum-Containing Nicotinic Acid Hydroxylase from <i>Clostridium</i> <i>barkeri</i>
  作者：Vadim N. Gladyshev、Sergei V. Khangulov、Thressa C. Stadtman

  DOI：10.1021/bi951793i

  日期：1996.1.1

  inactivated by these compounds and also by sulfide. Cyanide, a common inhibitor of Mo-containing hydroxylases, does not affect NAH catalytic activity. The "as isolated" enzyme exhibits a Mo(V) EPR signal (2.067 signal) that was detected at early stages of purification. NAH exhibits a high substrate specificity toward electron donor substrates. The ability of a nicotinate analog to reduce NAH (disappearance

  NADP（+）偶联的烟酸羟化酶（NAH）已通过改进的纯化方案从巴氏梭状芽胞杆菌中纯化至近乎均一的水平，该方案可分离出毫克量的比活度更高的酶（此前报道过）。在甘油的存在下，NAH在碱性pH下最稳定。由四个不同亚基组成的蛋白质以不同分子量的形式存在。每160 kDa蛋白质启动子有5-7 Fe，1 FAD和1Mo。酶中的Mo与钼蝶呤的二核苷酸形式结合，并与硒配位。Mo（V），黄素自由基和两个Fe2S2簇可以用EPR光谱仪观察到。烟酸羟化酶活性必不可少的Se辅因子可以通过许多变性程序从NAH中作为一种反应性低分子量化合物释放出来。在酶的纯化和储存过程中，观察到了硒的平行损失和催化活性。添加硒化钠或硒代磷酸钠不能恢复该酶的催化活性。相反，NAH被这些化合物以及硫化物可逆地灭活。氰化物，一种常见的含Mo羟化酶抑制剂，不影响NAH催化活性。“分离的”酶表现出在纯化的早期阶段检测到的Mo（V）EPR信号（2
• Holcenberg J.S.; Tsai L., J Biol Chem, 1969, 0021-9258, 1204-11
  作者：Holcenberg J.S.、Tsai L.

  DOI：——

  日期：——
• Purification, characterization and gene cloning of 6-hydroxynicotinate 3-monooxygenase from Pseudomonas fluorescens TN5
  作者：Hideo Nakano、Marco Wieser、Byungserk Hurh、Takahiro Kawai、Toyokazu Yoshida、Tsuneo Yamane、Toru Nagasawa

  DOI：10.1046/j.1432-1327.1999.00124.x

  日期：1999.2.5

  6‐Hydroxynicotinate 3‐monooxygenase, a membrane‐bound, 42‐kDa monomeric enzyme from Pseudomonas fluorescens TN5 was purified and characterized. The enzyme catalyzes the oxidative decarboxylation of 6‐hydroxynicotinate and depends on O2, NADH and FAD with the holoenzyme containing 1 m of FAD per 1 m of enzyme. The isolated enzyme was used for the synthesis of 2,5‐dihydroxypyridine, a precursor for the chemical synthesis of 5‐aminolevulinic acid, which is applied as a plant growth hormone, a herbicide and in cancer therapy. A 1.8‐kbp DNA fragment, which contains the ORF encoding 6‐hydroxynicotinic acid 3‐monooxygenase, was cloned, sequenced and expressed in Escherichia coli. The deduced 385 amino acid sequence of the cloned ORF is in agreement with the enzyme molecular mass, amino acid sequence of an internal peptide, contains a putative FAD‐binding site and is homologous to similar flavoproteins such as salicylate 1‐monoxygenase.
• Cloning, heterologous expression, and functional characterization of the nicotinate dehydrogenase gene from Pseudomonas putida KT2440
  作者：Yao Yang、Sheng Yuan、Ting Chen、Pengjuan Ma、Guangdong Shang、Yijun Dai

  DOI：10.1007/s10532-008-9243-x

  日期：2009.7

  6-Hydroxynicotinate can be used for the production of drugs, pesticides and intermediate chemicals. Some Pseudomonas species were reported to be able to convert nicotinic acid to 6-hydroxynicotinate by nicotinate dehydrogenase. So far, previous reports on NaDH in Pseudomonas genus were confused and contradictory each other. Recently, Ashraf et al. reported an NaDH gene cloned from Eubacterium barkeri and suggested some deducted NaDH genes from other nine bacteria. But they did not demonstrate the activity of recombinant NaDH and did not mention NaDH gene in Pseudomonas. In this study we cloned the gene of NaDH, ndhSL, from Pseudomonas putida KT2440. NdhSL in P. putida KT2440 is composed of two subunits. The small subunit contains [2Fe2S] iron sulfur domain, while the large subunit contains domains of molybdenum cofactor and cytochrome c. Expression of recombinant ndhSL in P. entomophila L48, which lacks the ability to produce 6-hydroxynicotinate, enabled the resting cell and cell extract of engineering P. entomophila L48 to hydroxylate nicotinate. Gene knockout and recovery studies further confirmed the ndhSL function.