4-Amino-5-ammoniomethyl-2-methylpyrimidine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 4-Amino-5-ammoniomethyl-2-methylpyrimidine
• 英文别名: (4-amino-2-methylpyrimidin-5-yl)methylazanium
• 化学式: C6H11N4+
• 分子量: 139.18
• InChiKey: OZOHTVFCSKFMLL-UHFFFAOYSA-O

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  79.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-Amino-5-ammoniomethyl-2-methylpyrimidine 、 水 生成 4-氨基-5-羟基甲基-2-甲基嘧啶 、 铵
  参考文献：
  名称：

  硫胺素的新拯救途径

  摘要：

  硫胺素降解酶硫胺素II的生理功能已经使研究人员望而却步，已有50多年的历史了。在这里，我们证明了该酶与硫胺嘧啶的再生有关，而不是与硫胺降解有关，并且我们确定了挽救碱降解形式的硫胺的新途径。该途径广泛分布于细菌，古细菌和真核生物之间。在此途径中，使用ThiXYZ转运系统将硫胺素水解产物（例如N-甲酰基-4-氨基-5-氨基甲基-2-甲基嘧啶（甲酰氨基嘧啶； 15））转运到细胞中，并由ylmB编码的酰胺水解酶去甲酰化并水解4-氨基-5-羟甲基-2-甲基嘧啶（HMP; 6）-从头开始的中间体硫胺素的生物合成途径。据我们所知，这是硫胺素挽救途径的第一个例子，涉及通过辅助因子的一个杂环的降解而产生的硫胺素类似物。

  DOI：

  10.1038/nchembio.2007.13
• 作为产物：
  描述：

  水 、 4-氨基-5-(甲酰氨基甲基)-2-甲基嘧啶 生成 4-Amino-5-ammoniomethyl-2-methylpyrimidine 、 草氨酸
  参考文献：
  名称：

  硫胺素的新拯救途径

  摘要：

  硫胺素降解酶硫胺素II的生理功能已经使研究人员望而却步，已有50多年的历史了。在这里，我们证明了该酶与硫胺嘧啶的再生有关，而不是与硫胺降解有关，并且我们确定了挽救碱降解形式的硫胺的新途径。该途径广泛分布于细菌，古细菌和真核生物之间。在此途径中，使用ThiXYZ转运系统将硫胺素水解产物（例如N-甲酰基-4-氨基-5-氨基甲基-2-甲基嘧啶（甲酰氨基嘧啶； 15））转运到细胞中，并由ylmB编码的酰胺水解酶去甲酰化并水解4-氨基-5-羟甲基-2-甲基嘧啶（HMP; 6）-从头开始的中间体硫胺素的生物合成途径。据我们所知，这是硫胺素挽救途径的第一个例子，涉及通过辅助因子的一个杂环的降解而产生的硫胺素类似物。

  DOI：

  10.1038/nchembio.2007.13

文献信息

• Salvage of the thiamin pyrimidine moiety by plant TenA proteins lacking an active-site cysteine
  作者：Rémi Zallot、Mohammad Yazdani、Aymeric Goyer、Michael J. Ziemak、Jiahn-Chou Guan、Donald R. McCarty、Valérie de Crécy-Lagard、Svetlana Gerdes、Timothy J. Garrett、Jordi Benach、John F. Hunt、David K. Shintani、Andrew D. Hanson

  DOI：10.1042/bj20140522

  日期：2014.10.1

  cysteine, the other (TenA_E) not. TenA_C proteins participate in thiamin salvage by hydrolysing the thiamin breakdown product amino-HMP (4-amino-5-aminomethyl-2-methylpyrimidine) to HMP (4-amino-5-hydroxymethyl-2-methylpyrimidine); the function of TenA_E proteins is unknown. Comparative analysis of prokaryote and plant genomes predicted that (i) TenA_E has a salvage role similar to, but not identical with

  TenA 蛋白家族存在于原核生物、植物和真菌中；它有两个亚家族，一个 (TenA_C) 具有活性位点半胱氨酸，另一个 (TenA_E) 没有。TenA_C 蛋白通过将硫胺分解产物氨基-HMP (4-amino-5-aminomethyl-2-methylpyrimidine) 水解为 HMP (4-amino-5-hydroxymethyl-2-methylpyrimidine) 参与硫胺回收；TenA_E 蛋白的功能未知。原核生物和植物基因组的比较分析预测 (i) TenA_E 具有与 TenA_C 相似但不相同的补救作用，以及 (ii) TenA_E 和 TenA_C 也具有非补救作用，因为它们存在于不能制造硫胺素。重组拟南芥和玉米 TenA_E 蛋白 (At3g16990, GRMZM2G080501) 将氨基 HMP 水解为 HMP，并且更积极地将氨基 HMP 的 N-甲酰基衍生物水解为氨基
• Mutagenesis studies on TenA: A thiamin salvage enzyme from Bacillus subtilis
  作者：Amy L. Jenkins、Yang Zhang、Steven E. Ealick、Tadhg P. Begley

  DOI：10.1016/j.bioorg.2007.10.005

  日期：2008.2

  hydrolysis of 4-amino-5-aminomethyl-2-methylpyrimidine and participates in the salvage of base-degraded thiamin. Here, we describe mutagenesis of the active site of TenA guided by structures of the enzyme complexed to a substrate analog and to the product. Catalytic roles for each of the active site residues are identified and a mechanism for the reaction is described.

  TenA 催化 4-amino-5-aminomethyl-2-methylpyrimidine 的水解并参与碱降解硫胺素的回收。在这里，我们描述了由与底物类似物和产物复合的酶结构引导的 TenA 活性位点的诱变。确定了每个活性位点残基的催化作用，并描述了反应机制。
• Structural and mutational analysis of TenA protein (HP1287) from the Helicobacter pylori thiamin salvage pathway - evidence of a different substrate specificity
  作者：Nicola Barison、Laura Cendron、Alberto Trento、Alessandro Angelini、Giuseppe Zanotti

  DOI：10.1111/j.1742-4658.2009.07326.x

  日期：2009.11

  modest. Moreover, in the present study, we demonstrate that the mutation at residue 47, a position where a phenylalanine occurs in all the strains of H. pylori sequenced to date, is not sufficient to explain the very low catalytic activity toward the expected substrate. As a result of differences in the colonization environment of H. pylori as well as the TenA structural and catalytic peculiar features

  幽门螺杆菌的HP1287（tenA）包括在细菌定殖和持久性中起重要作用的基因中。该基因已被克隆，其产物蛋白TenA已被表达和纯化。分别以2.7和2.4Å的分辨率确定了野生型蛋白质和突变型F47Y的晶体结构。分子模型是具有222个对称性的同型四聚体，表明幽门螺杆菌TenA结构属于蛋白质的硫胺素II类。最近发现这些酶参与了硫胺素前体羟基嘧啶的合成的挽救途径，该途径构成了硫胺素生物合成的组成部分，特别是生活在土壤中的细菌。相比之下，来自H的TenA的酶促测量。幽门螺杆菌表明，对假定的底物4-氨基-5-氨基甲基-2-甲基嘧啶的活性非常适中。此外，在本研究中，我们证明了在迄今已测序的所有幽门螺杆菌菌株中，残基47（苯丙氨酸出现在苯丙氨酸的位置）处的突变不足以说明对预期底物的催化活性非常低。由于幽门螺杆菌的定居环境以及TenA结构和催化特性的差异，我们建议幽门螺杆菌酶在硫胺素的生物合成途径中可能起关键
• The 2.35 Å structure of the TenA homolog from<i>Pyrococcus furiosus</i>supports an enzymatic function in thiamine metabolism
  作者：Jordi Benach、William C. Edstrom、Insun Lee、Kalyan Das、Bonnie Cooper、Rong Xiao、Jinfeng Liu、Burkhard Rost、Thomas B. Acton、Gaetano T. Montelione、John F. Hunt

  DOI：10.1107/s0907444905005147

  日期：2005.5.1

  TenA (transcriptional enhancer A) has been proposed to function as a transcriptional regulator based on observed changes in gene-expression patterns when overexpressed in Bacillus subtilis. However, studies of the distribution of proteins involved in thiamine biosynthesis in different fully sequenced genomes have suggested that TenA may be an enzyme involved in thiamine biosynthesis, with a function related to that of the ThiC protein. The crystal structure of PF1337, the TenA homolog from Pyrococcus furiosus, is presented here. The protomer comprises a bundle of alpha-helices with a similar tertiary structure and topology to that of human heme oxygenase-1, even though there is no significant sequence homology. A solvent-sequestered cavity lined by phylogenetically conserved residues is found at the core of this bundle in PF1337 and this cavity is observed to contain electron density for 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate, the product of the ThiC enzyme. In contrast, the modestly acidic surface of PF1337 shows minimal levels of sequence conservation and a dearth of the basic residues that are typically involved in DNA binding in transcription factors. Without significant conservation of its surface properties, TenA is unlikely to mediate functionally important protein-protein or protein-DNA interactions. Therefore, the crystal structure of PF1337 supports the hypothesis that TenA homologs have an indirect effect in altering gene-expression patterns and function instead as enzymes involved in thiamine metabolism.
• Structural Characterization of the Regulatory Proteins TenA and TenI from <i>Bacillus subtilis</i> and Identification of TenA as a Thiaminase II^,
  作者：Angela V. Toms、Amy L. Haas、Joo-Heon Park、Tadhg P. Begley、Steven E. Ealick

  DOI：10.1021/bi0478648

  日期：2005.2.1

  Bacillus subtilis gene products TenA and TenI have been implicated in regulating the production of extracellular proteases, but their role in the regulation process remains unclear. The structural characterization of these proteins was undertaken to help provide insight into their function. We have determined the structure of TenA alone and in complex with 4-amino-2-methyl-5-hydroxymethylpyrimidine, and we demonstrate that TenA is a thiaminase II. The TenA structure suggests that the degradation of thiamin by TenA likely proceeds via the same addition-elimination mechanism described for thiaminase I. Three active-site residues, Asp44, Cys135, and Glu205, are likely involved in substrate binding and catalysis based on the enzyme/product complex structure and the conservation of these residues within TenA sequences. We have also determined the structure of TenI. Although TenI shows significant structural homology to thiamin phosphate synthase, it has no known enzymatic function. The structure suggests that TenI is unable to bind thiamin phosphate, largely resulting from the presence of leucine at position 119, while the corresponding residue in thiamin phosphate synthase is glycine.