dTDP-3-amino-2,3,6-trideoxy-4-keto-D-glucose | 321847-71-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 英文名称: dTDP-3-amino-2,3,6-trideoxy-4-keto-D-glucose
• 英文别名: dTDP-3-amino-2,3,6-trideoxy-D-threo-hexopyranos-4-ulose；[(2R,4R,6R)-4-amino-6-methyl-5-oxooxan-2-yl] [hydroxy-[[(2R,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy]phosphoryl] hydrogen phosphate
• CAS: 321847-71-6
• 化学式: C₁₆H₂₅N₃O₁₃P₂
• 分子量: 529.334
• InChiKey: IVWGOICUSBJICO-OJEZURLMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.9
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  234
• 氢给体数：
  5
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  dTDP-3-amino-2,3,6-trideoxy-4-keto-D-glucose 、 S-腺苷-L-蛋氨酸 在 L-谷氨酸 、 2,3-dehydratase 、 3-aminotransferase 、 4,6-dehydratase 、 micromonospora chalcea C-3'-methyltransferase 、 甘油 、 sodium chloride 作用下， 以 水 为溶剂， 生成 thymidine-5'-diphosphate-3-amino-2,3,6-trideoxy-3-C-methyl-D-erythro-hexopyranos-4-ulose
  参考文献：
  名称：

  Molecular Architecture of a C-3′-Methyltransferase Involved in the Biosynthesis of d-Tetronitrose

  摘要：

  S-Adenosylmethionine (SAM)-dependent methyltransferases are involved in a myriad of biological processes, including signal transduction, chromatin repair, metabolism, and biosyntheses, among others. Here we report the high-resolution structure of a novel C-3'-methyltransferase involved in the production of D-tetronitrose, an unusual sugar found attached to the antitumor agent tetrocarcin A or the antibiotic kijanimicin. Specifically, this enzyme, referred to as TcaB9 and cloned from Micromonospora chalcea, catalyzes the conversion of dTDP-3-amino-2,3,6-trideoxy-4-keto-D-glucose to dTDP-3-amino-2,3,6-trideoxy-4-keto-3-methyl-D-glucose. For this analysis, two structures were determined to 1.5 angstrom resolution: one in which the enzyme was crystallized in the presence of SAM and dTMP and the other with the protein complexed to S-adenosylhomocysteine and its dTDP-linked sugar product. The overall fold of the monomeric enzyme can be described in terms of three domains. The N-terminal domain harbors the binding site for a zinc ion that is ligated by four cysteines. The middle domain adopts the canonical "SAM-binding" fold with a seven-stranded mixed beta-sheet flanked on either side by three alpha-helices. This domain is responsible for anchoring the SAM cofactor to the protein. Strikingly, the C-terminal domain also contains a seven-stranded beta-sheet, and it appears to be related to the middle domain by an approximate 2-fold rotational axis, thus suggesting TcaB9 arose via gene duplication. Key residues involved in sugar binding include His 181, Glu 224, His 225, and Tyr 222. Their possible roles in catalysis are discussed.

  DOI：

  10.1021/bi100782b

文献信息

• Molecular Architecture of a <i>C-</i>3′-Methyltransferase Involved in the Biosynthesis of <scp>d</scp>-Tetronitrose
  作者：Nathan A. Bruender、James B. Thoden、Manpreet Kaur、Marie K. Avey、Hazel M. Holden

  DOI：10.1021/bi100782b

  日期：2010.7.20

  S-Adenosylmethionine (SAM)-dependent methyltransferases are involved in a myriad of biological processes, including signal transduction, chromatin repair, metabolism, and biosyntheses, among others. Here we report the high-resolution structure of a novel C-3'-methyltransferase involved in the production of D-tetronitrose, an unusual sugar found attached to the antitumor agent tetrocarcin A or the antibiotic kijanimicin. Specifically, this enzyme, referred to as TcaB9 and cloned from Micromonospora chalcea, catalyzes the conversion of dTDP-3-amino-2,3,6-trideoxy-4-keto-D-glucose to dTDP-3-amino-2,3,6-trideoxy-4-keto-3-methyl-D-glucose. For this analysis, two structures were determined to 1.5 angstrom resolution: one in which the enzyme was crystallized in the presence of SAM and dTMP and the other with the protein complexed to S-adenosylhomocysteine and its dTDP-linked sugar product. The overall fold of the monomeric enzyme can be described in terms of three domains. The N-terminal domain harbors the binding site for a zinc ion that is ligated by four cysteines. The middle domain adopts the canonical "SAM-binding" fold with a seven-stranded mixed beta-sheet flanked on either side by three alpha-helices. This domain is responsible for anchoring the SAM cofactor to the protein. Strikingly, the C-terminal domain also contains a seven-stranded beta-sheet, and it appears to be related to the middle domain by an approximate 2-fold rotational axis, thus suggesting TcaB9 arose via gene duplication. Key residues involved in sugar binding include His 181, Glu 224, His 225, and Tyr 222. Their possible roles in catalysis are discussed.