NADP⁺ | 165676-60-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - （5'->5'）-二核苷酸
• 英文名称: NADP⁺
• 英文别名: NADPH；nicotinamide adenine dinucleotide phosphate；coenzyme II；[(2R,3R,4R,5R)-2-(6-aminopurin-9-yl)-5-[[[[(2R,3S,4R,5R)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl]oxy-oxidophosphoryl]oxymethyl]-4-hydroxyoxolan-3-yl] phosphate
• CAS: 165676-60-8
• 化学式: C₂₁H₂₅N₇O₁₇P₃
• 分子量: 740.387
• InChiKey: XJLXINKUBYWONI-NNYOXOHSSA-K

计算性质

• 辛醇/水分配系数(LogP)：
  -7.3
• 重原子数：
  48
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  376
• 氢给体数：
  5
• 氢受体数：
  21

反应信息

• 作为反应物：
  描述：

  NADP⁺ 生成 2'-phospho-cyclic ADP-ribose 、 烟酰胺
  参考文献：
  名称：

  CD38是负责在哺乳动物组织中合成烟酸-腺嘌呤二核苷酸磷酸的主要酶。

  摘要：

  在本研究中，我们已经确定了在释放Ca（2+）的核苷酸烟酸-腺嘌呤二核苷酸磷酸（NAADP）合成酶CD38的作用。在大鼠组织中，我们观察到可以使用抗CD38抗体与CD38共免疫沉淀NAADP合成的能力。此外，我们观察到来自CD38基因敲除小鼠的几种组织不具有合成该核苷酸的能力。另外，CD38也被鉴定为负责合成第二信使环ADP-核糖的主要酶。这些观察结果得出结论，CD38是负责NAADP和环状ADP-核糖合成的主要酶，并增加了新的信号传导途径的可能性，其中同一酶合成了两个不同的Ca（2+）释放核苷酸。

  DOI：

  10.1042/0264-6021:3620125
• 作为产物：
  描述：

  nicotinamide adenine dinucleotide 、 NADPH(4-) 生成 NADH 、 NADP⁺
  参考文献：
  名称：

  Link between the Membrane-Bound Pyridine Nucleotide Transhydrogenase and Glutathione-Dependent Processes in Rhodobacter sphaeroides

  摘要：

  摘要 兼性光营养体中存在依赖谷胱甘肽的甲醛氧化途径 中存在依赖谷胱甘肽的甲醛氧化途径。 中存在依赖于谷胱甘肽的甲醛氧化途径，从而确定了有助于甲醛代谢的基因产物。缺乏谷胱甘肽依赖性甲醛脱氢酶（GSH-FDH）的突变体对甲醛代谢源（如甲醇）很敏感。这种生长表型与甲醛氧化缺陷有关。另外还分离出了对甲醇敏感的突变体，这些突变体含有 Tn 5 插入物的 pntA 中含有 Tn 5 插入物的其他甲醇敏感突变体，该突变体编码膜结合吡啶核苷酸转氢酶的 α 亚基。缺乏转氢酶活性的突变体具有不同于缺乏 GSH-FDH 活性的突变体的表型和生理特征。例如，缺乏转氢酶活性的细胞可以在无氧条件下利用甲醇作为唯一的碳源，并且不会出现甲醛氧化缺陷。 13 C 核磁共振测定。由于反式氢化酶可能是 NADPH 的主要来源，失去这种酶可能导致需要这种化合物的另一种来源。支持这一假设的证据包括其他产生 NADPH 的酶的特异性活性增加，以及发现通过 Entner-Doudoroff 途径利用葡萄糖可恢复缺乏转氢酶活性的细胞对有氧甲醇的抗性。缺乏转氢酶活性的突变体在有氧条件下的谷胱甘肽二硫化物水平也较高，因此这种菌株对氧化应激剂（如二酰胺）的敏感性增加是一致的，众所周知，氧化应激剂会改变谷胱甘肽池的氧化还原状态。在有氧条件下，细胞需要谷胱甘肽来维持 GSH-FDH 的活性和修复氧化损伤的蛋白质，因此将提出一个模型来解释反式氢化酶的作用。

  DOI：

  10.1128/jb.184.2.400-409.2002

文献信息

• Characterization of Two Isoforms of Mouse 3(17).ALPHA.-Hydroxysteroid Dehydrogenases of the Aldo-Keto Reductase Family
  作者：Syuhei Ishikura、Noriyuki Usami、Satoko Nakajima、Akiko Kameyama、Hiroaki Shiraishi、Vincenzo Carbone、Ossama El-Kabbani、Akira Hara

  DOI：10.1248/bpb.27.1939

  日期：——

  Mouse kidney contains two 3(17)α-hydroxysteroid dehydrogenases (HSDs) that show essentially the same properties except for their isoelectric points. However, the structural differences and physiological roles of the two enzymes remain unknown. In this study, we have isolated cDNAs for the two 3(17)α-HSDs from a total RNA sample of mouse kidney by reverse transcription-PCR. The identity of the cDNAs was confirmed by characterization of the recombinant enzymes that showed the same molecular weights, pI values, pH optima, substrate specificity and inhibitor sensitivity as those of the enzymes from mouse kidney. We also found that the recombinant enzymes reduce precursors of neuroactive progesterone derivatives, 5α-dihydrotestoserone, deoxycorticosterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate and estrone at low Km values of 0.3—2 μM. The two enzymes belonged to the aldo-keto reductase (AKR) family, and their 323-amino acid sequences differed only by five amino acids. The sequences of the two isoforms are identical to those of proteins that are predicted to be encoded in a gene for AKR1C21 in the database of the mouse genome. However, the mRNAs for the two isoforms were expressed in mouse kidney and other tissues, in which their expression levels were different. The results indicate an important role of 3(17)α-HSD in controlling the concentrations of various steroid hormones in the mouse tissues, and suggest the existence of two genes for the two isoforms of the enzyme.

  小鼠肾脏含有两种3(17)α-羟基类固醇脱氢酶(HSD)，它们的基本性质相同，除了等电点不同。然而，这两种酶的结构差异和生理作用仍然未知。在本研究中，我们通过逆向转录-PCR从小鼠肾脏总RNA样本中分离得到了两种3(17)α-HSD的cDNA。通过重组酶的特性鉴定确认了cDNA的身份，这些重组酶显示出与小鼠肾脏来源酶相同的分子量、等电点、pH最适值、底物特异性和抑制剂敏感性。我们还发现，这些重组酶能以低Km值0.3—2 μM还原神经活性孕酮衍生物前体、5α-二氢睾酮、去氧皮质酮、脱氢表雄酮、脱氢表雄酮硫酸酯和雌酮。这两种酶属于醛酮还原酶（AKR）家族，它们的323个氨基酸序列仅相差五个氨基酸。这两种异构体的序列与预测在老鼠基因组数据库中的AKR1C21基因编码的蛋白质序列一致。然而，这两种异构体的mRNA在小鼠肾脏和其他组织中表达，其表达水平不同。结果表明，3(17)α-HSD在小鼠组织中控制各种类固醇激素的浓度中起着重要作用，并提示这两种酶异构体存在两种基因。
• Enzyme-Catalyzed Intramolecular Enantioselective Hydroalkoxylation
  作者：Shu-Shan Gao、Marc Garcia-Borràs、Joyann S. Barber、Yang Hai、Abing Duan、Neil K. Garg、K. N. Houk、Yi Tang

  DOI：10.1021/jacs.7b01089

  日期：2017.3.15

  method of forming C-O bonds and cyclic ethers in synthetic chemistry. In studying the biosynthesis of the fungal natural product herqueinone, we identified an enzyme that can perform an intramolecular enantioselective hydroalkoxylation reaction. PhnH catalyzes the addition of a phenol to the terminal olefin of a reverse prenyl group to give a dihydrobenzofuran product. The enzyme accelerates the reaction

  氢烷氧基化是合成化学中形成 CO 键和环醚的一种强大而有效的方法。在研究真菌天然产物 Herqueinone 的生物合成过程中，我们确定了一种可以进行分子内对映选择性加氢烷氧基化反应的酶。PhnH 催化苯酚加成到反向异戊二烯基的末端烯烃，得到二氢苯并呋喃产物。与未催化的反应相比，该酶将反应加速了 3 × 105 倍。PhnH 属于具有未知功能域 (DUF3237) 的蛋白质超家族，其中没有成员具有先前已验证的功能。PhnH 的发现表明酶可用于促进对映选择性加氢烷氧基化反应并形成环醚。
• Biocatalytic Characterization of Human FMO5: Unearthing Baeyer–Villiger Reactions in Humans
  作者：Filippo Fiorentini、Martina Geier、Claudia Binda、Margit Winkler、Kurt Faber、Mélanie Hall、Andrea Mattevi

  DOI：10.1021/acschembio.5b01016

  日期：2016.4.15

  physiological role) has long remained unexplored. In this study, we demonstrate the atypical in vitro activity of human FMO5 as a Baeyer–Villiger mono-oxygenase on a broad range of substrates, revealing the first example to date of a human protein catalyzing such reactions. The isolated and purified protein was active on diverse carbonyl compounds, whereas soft nucleophiles were mostly non- or poorly

  含黄素的单加氧酶被称为有效的药物代谢酶，为经过充分研究的细胞色素P450单加氧酶提供补充功能。虽然人类FMO同工型通常参与软亲核试剂的氧化，但人类FMO5的生物催化活性（及其生理作用）长期以来尚未得到开发。在这项研究中，我们证明了非典型的体外FMO5作为Baeyer-Villiger单加氧酶在多种底物上的活性，揭示了迄今为止人类蛋白催化此类反应的第一个例子。分离和纯化的蛋白质对多种羰基化合物具有活性，而柔软的亲核试剂大多不具有反应性或反应性较差。到目前为止，典型特征序列基序的缺失使人类FMO5与所有特征化的Baeyer-Villiger单加氧酶不同。这些发现为人类的氧化代谢开辟了新的前景。
• Discovery of the curcumin metabolic pathway involving a unique enzyme in an intestinal microorganism
  作者：Azam Hassaninasab、Yoshiteru Hashimoto、Kaori Tomita-Yokotani、Michihiko Kobayashi

  DOI：10.1073/pnas.1016217108

  日期：2011.4.19

  Polyphenol curcumin, a yellow pigment, derived from the rhizomes of a plant ( Curcuma longa Linn) is a natural antioxidant exhibiting a variety of pharmacological activities and therapeutic properties. It has long been used as a traditional medicine and as a preservative and coloring agent in foods. Here, curcumin-converting microorganisms were isolated from human feces, the one exhibiting the highest activity being identified as Escherichia coli . We are thus unique in discovering that E. coli was able to act on curcumin. The curcumin-converting enzyme was purified from E. coli and characterized. The native enzyme had a molecular mass of about 82 kDa and consisted of two identical subunits. The enzyme has a narrow substrate spectrum, preferentially acting on curcumin. The microbial metabolism of curcumin by the purified enzyme was found to comprise a two-step reduction, curcumin being converted NADPH-dependently into an intermediate product, dihydrocurcumin, and then the end product, tetrahydrocurcumin. We named this enzyme “NADPH-dependent curcumin/dihydrocurcumin reductase” (CurA). The gene ( curA ) encoding this enzyme was also identified. A homology search with the BLAST program revealed that a unique enzyme involved in curcumin metabolism belongs to the medium-chain dehydrogenase/reductase superfamily.

  多酚姜黄素是一种来源于植物根茎（姜黄）的黄色色素，是一种天然抗氧化剂，展现出多种药理活性和治疗特性。长期以来，它一直被用作传统药物，以及食品的防腐剂和着色剂。在这里，从人类粪便中分离出了转化姜黄素的微生物，其中表现出最高活性的被鉴定为大肠杆菌。因此，我们发现大肠杆菌能够作用于姜黄素是独特的。从大肠杆菌中纯化并表征了转化姜黄素的酶。原生酶的分子量约为82 kDa，由两个相同的亚基组成。该酶具有狭窄的底物谱，优先作用于姜黄素。通过纯化酶对姜黄素的微生物代谢发现，包括一个两步还原过程，姜黄素首先以NADPH为辅助转化为一个中间产物，二氢姜黄素，然后形成最终产物四氢姜黄素。我们将这种酶命名为“NADPH依赖的姜黄素/二氢姜黄素还原酶”（CurA）。还鉴定了编码这种酶的基因（curA）。通过BLAST程序进行同源搜索，发现参与姜黄素代谢的独特酶属于中链脱氢酶/还原酶超家族。
• Purification and Characterization of NfrA1, a<i>Bacillus subtilis</i>Nitro/flavin Reductase Capable of Interacting with the Bacterial Luciferase
  作者：Shuhei ZENNO、Toshiro KOBORI、Masaru TANOKURA、Kaoru SAIGO

  DOI：10.1271/bbb.62.1978

  日期：1998.1

  ipa-43d is a hypothetical gene identified by the Bacillus subtilis genome project (Mol. Microbiol. 10, 371-384 1993; Nature 390, 249-256 1997). The ipa-43d protein overexpressed in E. coli was purified to homogeneity and its properties were analyzed biochemically. The ipa-43d protein was found to be tightly associated with FMN and to be capable of reducing both nitrofurazone and FMN effectively. Although the ipa-43d protein catalysis obeys the ping-pong Bi-Bi mechanism, catalysis mode was changed to the sequential mechanism upon coupling with the bioluminescent reaction. Database search showed that B. subtilis possessed four genes (ipa-44d, ytmO, yddN, and yvbT), encoding proteins similar in amino acid sequence to LuxA and LuxB of Photobacterium fischeri, and, in particular, ipa-44d is immediately adjacent to the ipa-43d gene on the chromosome.

  ipa-43d是一种假设的基因，由枯草芽孢杆菌基因组项目所识别（Mol. Microbiol. 10, 371-384 1993; Nature 390, 249-256 1997）。在E. coli中过量表达的ipa-43d蛋白被纯化至均一性，并对它的生化特性进行了分析。研究表明，ipa-43d蛋白紧密结合FMN，并能有效地还原硝基呋喃嗪和FMN。尽管ipa-43d蛋白的催化作用遵循乒乓式双双机制，但与生物发光反应耦合后，催化模式转变为连续机制。数据库搜索显示，枯草芽孢杆菌拥有四个基因（ipa-44d、ytmO、yddN和yvbT），这些基因编码的蛋白质与费氏光杆菌的LuxA和LuxB在氨基酸序列上相似，特别是ipa-44d基因位于染色体上紧邻ipa-43d基因的位置。