N,N'-bis(3-ammoniopropyl)butane-1,4-diaminium

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N,N'-bis(3-ammoniopropyl)butane-1,4-diaminium
• 英文别名: 3-azaniumylpropyl-[4-(3-azaniumylpropylazaniumyl)butyl]azanium
• 化学式: C10H30N4+4
• 分子量: 206.37
• InChiKey: PFNFFQXMRSDOHW-UHFFFAOYSA-R

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  14
• 可旋转键数：
  11
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  88.5
• 氢给体数：
  4
• 氢受体数：
  0

反应信息

• 作为反应物：
  描述：

  S-Adenosyl-L-methioninamine 、 N,N'-bis(3-ammoniopropyl)butane-1,4-diaminium 生成 氢(+1)阳离子 、 N(4)-aminopropylspermine(5+) 、 甲硫腺苷
  参考文献：
  名称：

  鉴定一种参与超嗜热菌中支链多胺合成的新型氨基丙基转移酶。

  摘要：

  长链和/或支链多胺是在嗜热菌中发现的独特聚阳离子。N(4)-氨基丙基精胺被认为是科达卡热球菌中的主要多胺。为了确定季支化五胺、N(4)-双（氨基丙基）亚精胺（N(4)-氨基丙基精胺的异构体）是否也存在，通过高压液相色谱、气相色谱分析酸提取的细胞质多胺色谱法 (HPLC) 和气相色谱-质谱法。N(4)-bis(aminopropyl)spermidine 是该物种中丰富的细胞质多胺。为了确定催化 N(4)-双(氨基丙基)亚精胺合成的酶，从细胞质中浓缩活性部分，并在 MASCOT 数据库分析后通过线性离子阱飞行时间质谱仪与电喷雾电离仪器进行分析。TK0545，TK0548、TK0967和TK1691被鉴定为候选酶，相应的基因被单独克隆并在大肠杆菌中表达。纯化重组形式，并测量其 N(4)-双 (氨基丙基) 亚精胺合成活性。在四个候选中，发现 TK1691 (BpsA) 可通过 N(4)-氨基丙基亚精胺从亚精胺合成

  DOI：

  10.1128/jb.01515-14
• 作为产物：
  描述：

  水 、 N(1)-acetylsperminium(3+) 生成 乙酸盐 、 N,N'-bis(3-ammoniopropyl)butane-1,4-diaminium
  参考文献：
  名称：

  Substrate specificity and function of acetylpolyamine amidohydrolases from Pseudomonas aeruginosa

  摘要：

  lation酶解作用。

  DOI：

  10.1186/s12858-016-0063-z

文献信息

• Heterologous Expression and Biochemical Characterization of a Polyamine Oxidase from Arabidopsis Involved in Polyamine Back Conversion
  作者：Paraskevi Tavladoraki、Marianna Nicoletta Rossi、Giuseppe Saccuti、Miguel Angel Perez-Amador、Fabio Polticelli、Riccardo Angelini、Rodolfo Federico

  DOI：10.1104/pp.106.080911

  日期：2006.8.1

  Polyamine oxidase (PAO) is a flavin adenine dinucleotide-dependent enzyme involved in polyamine catabolism. Animal PAOs oxidize spermine (Spm), spermidine (Spd), and/or their acetyl derivatives to produce H2O2, an aminoaldehyde, and Spd or putrescine, respectively, thus being involved in a polyamine back-conversion pathway. On the contrary, plant PAOs that have been characterized to date oxidize Spm and Spd to produce 1,3-diaminopropane, H2O2, and an aminoaldehyde and are therefore involved in the terminal catabolism of polyamines. A database search within the Arabidopsis (Arabidopsis thaliana) genome sequence showed the presence of a gene (AtPAO1) encoding for a putative PAO with 45% amino acid sequence identity with maize (Zea mays) PAO. The AtPAO1 cDNA was isolated and cloned in a vector for heterologous expression in Escherichia coli. The recombinant protein was purified by affinity chromatography on guazatine-Sepharose 4B and was shown to be a flavoprotein able to oxidize Spm, norspermine, and N1-acetylspermine with a pH optimum at 8.0. Analysis of the reaction products showed that AtPAO1 produces Spd from Spm and norspermidine from norspermine, demonstrating a substrate oxidation mode similar to that of animal PAOs. To our knowledge, AtPAO1 is the first plant PAO reported to be involved in a polyamine back-conversion pathway.

  多胺氧化酶（PAO）是一种依赖于黄素腺嘌呤二核苷酸的酶，参与多胺降解。动物PAOs氧化精胺（Spm）、亚精胺（Spd）和/或它们的乙酰衍生物，产生H2O2、氨基醛和Spd或腐胺，因此参与多胺回转途径。相反，到目前为止已经表征的植物PAOs氧化Spm和Spd，产生1,3-二氨基丙烷、 和氨基醛，因此参与多胺的末端降解。在拟南芥（拟南芥）基因组序列中进行数据库搜索，显示存在一个编码推测PAO的基因（AtPAO1），其氨基酸序列同玉米（玉米）PAO具有45％的同源性。 AtPAO1 cDNA被分离并克隆到Escherichia coli的载体中进行异源表达。亲和层析在guazatine-Sepharose 4B上纯化重组蛋白，并显示为一种能够在pH 8.0下氧化Spm、norspermine和N1-acetylspermine的黄素蛋白。反应产物的分析表明，AtPAO1从Spm产生Spd，从norspermine产生norspermidine，证明其底物氧化模式类似于动物PAOs。据我们所知，AtPAO1是首个报道参与多胺回转途径的植物PAO。

• Acetylpolyamine amidohydrolase from Mycoplana ramosa: gene cloning and characterization of the metal-substituted enzyme
  作者：K Sakurada、T Ohta、K Fujishiro、M Hasegawa、K Aisaka

  DOI：10.1128/jb.178.19.5781-5786.1996

  日期：1996.10

  We have cloned a gene (aphA) encoding acetylpolyamine amidohydrolase from Mycoplana ramosa ATCC 49678, (previously named Mycoplana bullata). A genomic library of M. ramosa was screened with an oligonucleotide probe designed from a N-terminal amino acid sequence of the enzyme purified from M. ramosa. Nucleotide sequence analysis revealed an open reading frame of 1,023 bp which encodes a polypeptide with a molecular mass of 36,337 Da. This is the first report of the structure of acetylpolyamine amidohydrolase. The aphA gene was subcloned under the control of the trc promoter and was expressed in Escherichia coli MM294. The recombinant enzyme was purified, and the enzymatic properties were characterized. Substrate specificities, Km values, and Vmax values were identical to those of the native enzyme purified from M. ramosa. In the analysis of the metal-substituted enzymes, we found that the acid limb of pH rate profiles shifts from 7.2 for the original zinc enzyme to 6.6 for the cobalt enzyme. This change suggests that the zinc atom is essential for the catalytic activity of the enzyme similarly to the zinc atom in carboxypeptidase A.

  我们已经克隆了一个来自Mycoplana ramosa ATCC 49678（之前被称为Mycoplana bullata）的编码乙酰多胺酰胺水解酶的基因（aphA）。使用从M. ramosa中纯化的酶N末端氨基酸序列设计的寡核苷酸探针筛选了M. ramosa的基因组文库。核苷酸序列分析揭示了一个长1023个碱基的开放阅读框架，编码一个分子量为36,337 Da的多肽。这是有关乙酰多胺酰胺水解酶结构的首次报道。aphA基因在trc启动子的控制下亚克隆，并在大肠杆菌MM294中表达。重组酶被纯化，并对其酶学性质进行了表征。底物特异性，Km值和Vmax值与从M. ramosa中纯化的天然酶相同。在金属替代酶的分析中，我们发现pH速率曲线的酸性端从原始锌酶的7.2转移到钴酶的6.6。这种变化表明锌原子对于酶的催化活性至关重要，类似于羧肽酶A中的锌原子。
• Aminopropyltransferases: Function, Structure and Genetics
  作者：Yoshihiko Ikeguchi、Maria C. Bewley、Anthony E. Pegg

  DOI：10.1093/jb/mvj019

  日期：2006.1.1

  Aminopropyltransferases use decarboxylated S-adenosylmethionine as an aminopropyl donor and an amine acceptor to form polyamines. This review covers their structure, mechanism of action, inhibition, regulation and function. The best known aminopropyltransferases are spermidine synthase and spermine synthase but other members of this family including an N1-aminopropylagmatine synthase have been characterized. Spermidine synthase is an essential gene in eukaryotes and is very widely distributed. Key regions in the active site, which are very highly conserved, were identified by structural studies with spermidine synthase from Thermotoga maritima bound to S-adenosyl-1,8-diamino-3-thiooctane, a multisubstrate analog inhibitor. A general mechanism for catalysis by aminopropyltransferases can be proposed based on these studies. Spermine synthase is less widely distributed and is not essential for growth in yeast. However, Gy mice lacking spermine synthase have multiple symptoms including a profound growth retardation, sterility, deafness, neurological abnormalities and a propensity to sudden death, which can all be prevented by transgenic expression of spermine synthase. A large reduction in spermine synthase in human males due to a splice site variant causes Snyder-Robinson syndrome with mental retardation, hypotonia and skeletal abnormalities.

  氨丙基转移酶利用脱羧的 S-腺苷蛋氨酸作为氨丙基供体和胺受体，形成多胺。本综述涵盖它们的结构、作用机制、抑制、调节和功能。最著名的氨丙基转移酶是亚精胺合成酶和精胺合成酶，但该家族的其他成员，包括 N1-氨丙基巴马汀合成酶也已定性。精胺合成酶是真核生物的重要基因，分布非常广泛。通过对来自海洋嗜热菌（Thermotoga maritima）的精胺合成酶与 S-腺苷-1,8-二氨基-3-硫辛烷（一种多底物类似物抑制剂）结合的结构研究，确定了其活性位点中高度保守的关键区域。基于这些研究，可以提出氨丙基转移酶催化的一般机制。精胺合成酶分布较少，而且不是酵母生长所必需的。然而，缺乏精胺合成酶的 Gy 小鼠会出现多种症状，包括极度生长迟缓、不育、耳聋、神经系统异常和猝死倾向，这些症状都可以通过转基因表达精胺合成酶来预防。人类男性精氨酸合成酶因剪接位点变异而大量减少，会导致斯奈德-罗宾逊综合征（Snyder-Robinson Syndrome），表现为智力迟钝、肌张力低下和骨骼异常。
• Kinetic properties of spermine synthase from bovine brain
  作者：R L Pajula

  DOI：10.1042/bj2150669

  日期：1983.12.1

  A kinetic analysis including initial-velocity and product-inhibition studies were performed with spermine synthase purified from bovine brain. The enzyme activity was assayed in the presence of 5'-methylthioadenosine phosphorylase as an auxiliary enzyme to prevent the accumulation of the inhibitory product, 5'-methylthioadenosine, and thus to obtain linearity of the reaction with time. Initial-velocity

  使用从牛脑纯化的精胺合酶进行了动力学分析，包括初始速度和产物抑制研究。在5'-甲基硫代腺苷磷酸化酶作为辅助酶的存在下测定酶活性，以防止抑制产物5'-甲基硫代腺苷的积累，从而获得反应随时间的线性。初始速度研究给出了相交或收敛的线性双倒数图。在浓度高达0.4 mM时，未观察到脱羧S-腺苷甲硫氨酸对底物的抑制作用。亚精胺的表观米氏常数为60 microM，脱羧S-腺苷甲硫氨酸的表观Michaelis常数为0.1 microM。精胺是脱羧S-腺苷甲硫氨酸的竞争性产品抑制剂，但相对于另一种底物则是混合的，亚精胺。5'-甲基硫代腺苷对两种底物均表现出混合抑制作用，主要相对于脱羧化的S-腺苷甲硫氨酸具有竞争性，而对于亚精胺则主要不具有竞争性。观察到的动力学和抑制模式与强制性顺序机制一致，在强制性机制中，两种底物都可以在酶释放之前添加到酶中。
• Studies of inhibition of rat spermidine synthase and spermine synthase
  作者：Hiroshige Hibasami、Ronald T. Borchardt、Shiang Yuan Chen、James K. Coward、Anthony E. Pegg

  DOI：10.1042/bj1870419

  日期：1980.5.1

  at 30-45mum. 4. S-Adenosyl-l-homocysteine was a weak inhibitor of spermine synthase and practically inactive against spermidine synthase. Analogues of S-adenosylhomocysteine lacking either the carboxy or the amino group of the amino acid portion were somewhat more active, as were derivatives in which the ribose ring had been opened by oxidation. The sulphoxide and sulphone derivatives of decarboxylated

  1.测试了S-腺苷-1-蛋氨酸，S-腺苷-1-高半胱氨酸，5'-甲基硫代腺苷和分子中碱基，糖或氨基酸部分具有变化的许多类似物作为亚精胺合酶的潜在抑制剂和来自大鼠腹侧前列腺的精胺合酶。2.S-腺苷-1-甲硫氨酸对这些反应具有抑制作用，其他含centre中心的核苷也具有抑制作用。其中活性最高的是S-腺苷-1-蛋氨酸，S-腺苷-4-甲基硫代丁酸，S-腺苷-d-蛋氨酸和S-哌啶基甲硫氨酸，它们的活性均与S-腺苷甲硫氨酸本身相当，产生70-在1mm浓度下抑制98％。精胺合酶比亚精胺合酶更敏感。3. 5'-甲基硫代腺苷，5'-乙基硫代腺苷和5' -甲基硫代小球菌素都是这两种酶的有效抑制剂，在10-15mum抑制50％的精胺合酶，在30-45mum抑制50％的亚精胺合酶。4.S-腺苷-1-高半胱氨酸是精胺合酶的弱抑制剂，实际上对亚精胺合酶没有活性。缺少氨基酸部分的羧基或氨基的S-腺苷同型半胱氨酸的类似物