13CH3-AdoMet | 74084-24-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 5'-脱氧核糖核苷
• 英文名称: 13CH3-AdoMet
• 英文别名: methyl-13C-AdoMet；[S-¹³C-methyl]adenosyl-L-methionine；[methyl-¹³C]-SAM；[¹³C-methyl]-SAM；S-Adenosyl-L-methionine-13C；(2S)-2-amino-4-[[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-(113C)methylsulfonio]butanoate
• CAS: 74084-24-5
• 化学式: C₁₅H₂₂N₆O₅S
• 分子量: 399.432
• InChiKey: MEFKEPWMEQBLKI-NFZQFHNOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.26
• 重原子数：
  27.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  185.46
• 氢给体数：
  4.0
• 氢受体数：
  11.0

安全信息

• WGK Germany：
  3

反应信息

• 作为反应物：
  描述：

  13CH3-AdoMet 在 pyruvate formate-lyase activating enzyme, [4Fe−4S]⁺ state 作用下， 生成 5'-deoxyadenosyl radical
  参考文献：
  名称：

  难以捉摸的 5'-脱氧腺苷自由基：由 EPR 和 ENDOR 光谱捕获和表征

  摘要：

  5'-脱氧腺苷自由基 (5'-dAdo·) 提取底物 H 原子，作为由腺苷钴胺素依赖性和自由基 S-腺苷-l-甲硫氨酸 (RS) 酶催化的基于自由基的转化的第一步。尽管 5'-dAdo· 具有重要的生物学作用，但经过半个多世纪的努力，却一直未能对其进行表征。在这里，我们报告了在 12 K 的 RS 酶活性位点中产生 5'-dAdo· 的方法，该方法涉及从 [4Fe-4S]+ 簇到配位 S-腺苷甲硫氨酸 (SAM) 的低温光诱导电子转移以诱导均裂S-C5' 键断裂。我们通过使用带有同位素标记的电子顺磁共振 (EPR) 和电子核双共振 (ENDOR) 光谱明确揭示了这种长期寻找的自由基物种的结构，由密度泛函计算补充：平面 C5' (2pπ) 自由基（~70% 自旋占有率）；C5'(H)2 平面相对于 C5'-C4'-(C4'-H) 平面旋转了 ~37°（实验）/39°（DFT），...

  DOI：

  10.1021/jacs.9b05926
• 作为产物：
  描述：

  L-蛋氨酸-甲基-13C1 、 5’-三磷酸腺苷 在 methionine adenosyltransferase from Sulfolobus solfataricus 作用下， 以 aq. phosphate buffer 为溶剂， 反应 1.0h， 生成 13CH3-AdoMet
  参考文献：
  名称：

  CalS11（一种参与加利车霉素生物合成的 TDP-鼠李糖 3'-O-甲基转移酶）的结构和功能表征

  摘要：

  糖甲基转移酶 (MT) 是一类重要的定制酶，可催化甲基从S-腺苷-L-甲硫氨酸转移到糖基N- 、 C-和O-亲核试剂。虽然已发现参与天然产物生物合成的糖N-和C -MT在随后的糖基转移酶反应之前作用于糖核苷酸底物，但迄今为止研究的相应糖O-甲基化反应发生在糖基转移反应之后。在此，我们首次报告了使用1 H– 13 C-gHSQC 和同位素标记底物对来自棘孢小单孢菌的 TDP-3'- O-鼠李糖甲基转移酶 CalS11 进行的体外表征，并在 1.55 Å 分辨率下进行了 X 射线结构测定。这项研究强调了一种独特的基于 NMR 的甲基转移酶测定，表明 CalS11 是一种金属和一般酸/碱依赖性O -甲基转移酶，并且作为 TDP-己糖 - O -甲基转移酶的第一个晶体结构，为 TDP 己糖 - O -甲基转移酶提供了一个新模板机械研究和/或工程。

  DOI：

  10.1021/cb400068k

文献信息

• Direct Evidence for Methyl Group Coordination by Carbon-Oxygen Hydrogen Bonds in the Lysine Methyltransferase SET7/9
  作者：Scott Horowitz、Joseph D. Yesselman、Hashim M. Al-Hashimi、Raymond C. Trievel

  DOI：10.1074/jbc.m111.232876

  日期：2011.5

  SET domain lysine methyltransferases (KMTs) are S-adenosylmethionine (AdoMet)-dependent enzymes that catalyze the site-specific methylation of lysyl residues in histone and nonhistone proteins. Based on crystallographic and cofactor binding studies, carbon-oxygen (CH center dot center dot center dot O) hydrogen bonds have been proposed to coordinate the methyl groups of AdoMet and methyllysine within the SET domain active site. However, the presence of these hydrogen bonds has only been inferred due to the uncertainty of hydrogen atom positions in x-ray crystal structures. To experimentally resolve the positions of the methyl hydrogen atoms, we used NMR H-1 chemical shift coupled with quantum mechanics calculations to examine the interactions of the AdoMet methyl group in the active site of the human KMT SET7/9. Our results indicated that at least two of the three hydrogens in the AdoMet methyl group engage in CH center dot center dot center dot O hydrogen bonding. These findings represent direct, quantitative evidence of CH center dot center dot center dot O hydrogen bond formation in the SET domain active site and suggest a role for these interactions in catalysis. Furthermore, thermodynamic analysis of AdoMet binding indicated that these interactions are important for cofactor binding across SET domain enzymes.
• Electron-Nuclear Double Resonance Spectroscopic Evidence That <i>S</i>-Adenosylmethionine Binds in Contact with the Catalytically Active [4Fe−4S]⁺ Cluster of Pyruvate Formate-Lyase Activating Enzyme
  作者：Charles J. Walsby、Wei Hong、William E. Broderick、Jennifer Cheek、Danilo Ortillo、Joan B. Broderick、Brian M. Hoffman

  DOI：10.1021/ja012034s

  日期：2002.3.1

  Pyruvate formate-lyase activating enzyme (PFL-AE) is a representative member of an emerging family of enzymes that utilize iron-sulfur clusters and S-adenosylmethionine (AdoMet) to initiate radical catalysis. Although these enzymes have diverse functions, evidence is emerging that they operate by a common mechanism in which a [4Fe-4S](+) interacts with AdoMet to generate a 5'-deoxyadenosyl radical intermediate. To date, however, it has been unclear whether the iron-sulfur cluster is a simple electron-transfer center or whether it participates directly in the radical generation chemistry. Here we utilize electron paramagnetic resonance (EPR) and pulsed 35 GHz electron-nuclear double resonance (ENDOR) spectroscopy to address this question. EPR spectroscopy reveals a dramatic effect of AdoMet on the EPR spectrum of the [4Fe-4S]+ of PFL-AE, changing it from rhombic (g = 2.02, 1.94, 1.88) to nearly axial (g = 2.01, 1,88, 1.87). H-2 and C-13 ENDOR spectroscopy was performed on [4Fe-4S]+-PFL-AE (S = 1/2) in the presence of AdoMet labeled at the methyl position with either 2H or 13C (denoted [1+/AdoMet]). The observation of a substantial 2H coupling of similar to1 MHz (similar to6-7 MHz for H-1), as well as hyperfine-split signals from the 13C, manifestly require that AdoMet lie close to the cluster. 2H and 13C ENDOR data were also obtained for the interaction of AdoMet with the diamagnetic [4Fe-4S](2+) state of PFL-AE, which is visualized through cryoreduction of the frozen [4Fe-4S](2+)/AdoMet complex to form the reduced state (denoted [2+/AdoMet](red)) trapped in the structure of the oxidized state. H-2 and C-13 ENDOR spectra for [2+/AdoMet](red) are essentially identical to those obtained for the [1+/AdoMet] samples, showing that the cofactor binds in the same geometry to both the 1+ and 2+ states of PFL-AE. Analysis of 2D field-frequency 13C ENDOR data reveals an isotropic hyperfine contribution, which requires that AdoMet lie in contact with the cluster, weakly interacting with it through an incipient bond/antibond. From the anisotropic hyperfine contributions for the 2H and 13C ENDOR, we have estimated the distance from the closest methyl proton of AdoMet to the closest iron of the cluster to be similar to3.0-3.8 Angstrom, while the distance from the methyl carbon to the nearest iron is similar to4-5 Angstrom. We have used this information to construct a model for the interaction of AdoMet with the [4Fe-4S](2+/+) cluster of PFL-AE and have proposed a mechanism for radical generation that is consistent with these results.
• Isolation, structure, and genetically engineered synthesis of precorrin-5, the pentamethylated intermediate of vitamin B12 biosynthesis
  作者：Changhee Min、Barbara P. Atshaves、Charles A. Roessner、Neal J. Stolowich、Jonathan B. Spencer、A. Ian Scott

  DOI：10.1021/ja00075a072

  日期：1993.11