S-adenosyl-[methyl-d3]-methionine

• 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: S-adenosyl-[methyl-d3]-methionine
• 英文别名: S-(5'-Adenosyl)-L-methionine-d3；(2S)-4-[[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-(trideuteriomethyl)sulfonio]-2-azaniumylbutanoate
• 化学式: C₁₅H₂₃N₆O₅S
• 分子量: 402.427
• InChiKey: MEFKEPWMEQBLKI-JSJAHMFWSA-O

计算性质

• 辛醇/水分配系数(LogP)：
  -3.5
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  184
• 氢给体数：
  5
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  S-adenosyl-[methyl-d3]-methionine 在 Escherichia coli RlmN 、 三羟甲基氨基甲烷盐酸盐 、 magnesium chloride 作用下， 以 水 为溶剂， 生成 S-(5'-腺苷)-L-高半胱氨酸
  参考文献：
  名称：

  Cfr and RlmN Contain a Single [4Fe-4S] Cluster, which Directs Two Distinct Reactivities for S-Adenosylmethionine: Methyl Transfer by S_N2 Displacement and Radical Generation

  摘要：

  The radical SAM (RS) proteins RlmN and Cfr catalyze methylation of carbons 2 and 8, respectively, of adenosine 2503 in 235 rRNA. Both reactions are similar in scope, entailing the synthesis of a methyl group partially derived from S-adenosylmethionine (SAM) onto electrophilic sp(2)-hybridized carbon atoms via the intermediacy of a protein S-methylcysteinyl (mCys) residue. Both proteins contain five conserved Cys residues, each required for turnover. Three cysteines lie in a canonical RS CxxxCxxC motif and coordinate a [4Fe-4S]-cluster cofactor; the remaining two are at opposite ends of the polypeptide. Here we show that each protein contains only the one "radical SAM" [4Fe-4S] cluster and the two remaining conserved cysteines do not coordinate additional iron-containing species. In addition, we show that, while wild-type RlmN bears the C355 mCys residue in its as-isolated state, RlmN that is either engineered to lack the [4Fe-4S] duster by substitution of the coordinating cysteines or isolated from Escherichia coli cultured under iron-limiting conditions does not bear a C355 mCys residue. Reconstitution of the [4Fe-4S] cluster on wild-type apo RlmN followed by addition of SAM results in rapid production of S-adenosylhomocysteine (SAH) and the mCys residue, while treatment of apo RlmN with SAM affords no observable reaction. These results indicate that in Cfr and RlmN, SAM bound to the unique iron of the [4Fe-4S] duster displays two reactivities. It serves to methylate C355 of RlmN (C338 of Cfr), or to generate the 5'-deoxyadenosyl 5'-radical, required for substrate-dependent methyl synthase activity.

  DOI：

  10.1021/ja207327v
• 作为产物：
  描述：

  L-甲硫氨酸-甲基-d3 、 5'-氯-5'-脱氧腺苷 在 enzyme SalL (Salinospora tropica) 、 Cleland's reagent 、 BSA 作用下， 以 aq. phosphate buffer 为溶剂， 反应 7.0h， 生成 S-adenosyl-[methyl-d3]-methionine
  参考文献：
  名称：

  串联酶促sp2-C-甲基化过程：原位S-腺苷-1-蛋氨酸形成与甲基转移偶联

  摘要：

  描述了一种单锅，两种酶的C-甲基化过程。组合使用SALL（SAM生产Salinospora tropica）与C-甲基NOVO（链霉菌spheroides）使一套甲基化和乙基香豆素产物的合成，这表现为标记13 CH 3，13 CD 3及CD 3组从它们相应的SAM类似物。

  DOI：

  10.1002/cbic.201700115

文献信息

• Capturing Intermediates in the Reaction Catalyzed by NosN, a Class C Radical <i>S</i>-Adenosylmethionine Methylase Involved in the Biosynthesis of the Nosiheptide Side-Ring System
  作者：Bo Wang、Joseph W. LaMattina、Savannah L. Marshall、Squire J. Booker

  DOI：10.1021/jacs.8b13157

  日期：2019.4.10

  of Glu6 of the core peptide and the nascent C1 unit. However, exactly when NosN performs its function during the biosynthesis of nosiheptide is unknown. Herein, we report the syntheses and use of three peptide mimics as potential substrates designed to address the timing of NosN's function. Our results show that NosN clearly closes the side ring before NosO forms the pyridine ring and most likely before

  那西肽是一种核糖体合成和翻译后修饰的硫肽天然产物，具有抗菌、抗癌和免疫抑制特性。它包含一个双环结构，由一个大环和一个独特的侧环系统组成，该系统包含一个 3,4-二甲基吲哚酸桥，分别通过酯键和硫酯键连接到核心肽的 Glu6 和 Cys8 的侧链。除了由 nosM 基因编码的结构肽外，侧环结构的生物合成还需要 NosI、-J、-K、-L 和 -N 的作用。NosN 被注释为 C 类自由基 S-腺苷甲硫氨酸 (SAM) 甲基化酶，但它的真正功能是将 C1 单元从 SAM 转移到 3-甲基-2-吲哚酸 (MIA) 的 C4 上，同时在核心肽的 Glu6 羧酸盐和新生的 C1 单元之间形成键。然而，在那西肽的生物合成过程中，NosN 究竟何时发挥其功能尚不清楚。在此，我们报告了三种肽模拟物作为潜在底物的合成和使用，旨在解决 NosN 功能的时间问题。我们的结果表明，NosN 在 NosO 形成吡啶环之前清楚地关闭了侧环，最有可能在
• Exploring the Biosynthetic Potential of TsrM, a B ₁₂ ‐dependent Radical SAM Methyltransferase Catalyzing Non‐radical Reactions
  作者：Feryel Soualmia、Alain Guillot、Nazarii Sabat、Clémence Brewee、Xavier Kubiak、Michael Haumann、Xavier Guinchard、Alhosna Benjdia、Olivier Berteau

  DOI：10.1002/chem.202200627

  日期：2022.6

  catalyzing methylation reactions from carbon-atoms to nucleophilic atoms making it a unique and versatile alkylating agent. TsrM is able to directly transfer methyl groups on the less reactive carbon atom of the indole ring and to install several methyl groups on its substrate. TsrM has thus unique properties among radical SAM enzymes by notably catalyzing non-radical reactions. (SAM: S-adenosyl-L-methionine)

  TsrM 是一种 B 12依赖性自由基 SAM 酶，可催化从碳原子到亲核原子的甲基化反应，使其成为一种独特且用途广泛的烷化剂。TsrM 能够直接转移吲哚环反应性较低的碳原子上的甲基，并在其底物上安装几个甲基。因此，通过显着催化非自由基反应，TsrM 在自由基 SAM 酶中具有独特的特性。（SAM：S-腺苷-L-蛋氨酸）。
• A Tandem Enzymatic sp² -C-Methylation Process: Coupling in Situ S-Adenosyl-<scp>l</scp> -Methionine Formation with Methyl Transfer
  作者：Joanna C. Sadler、Luke D. Humphreys、Radka Snajdrova、Glenn A. Burley

  DOI：10.1002/cbic.201700115

  日期：2017.6.1

  A one‐pot, two‐enzyme C‐methylation process is described. Combining SAM production using SalL (Salinospora tropica) with the C‐methyltransferase NovO (Streptomyces spheroides) enables the synthesis of a suite of methylated and ethylated coumarin products, as demonstrated for labelled 13CH3, 13CD3 and CD3 groups from their corresponding SAM analogues.

  描述了一种单锅，两种酶的C-甲基化过程。组合使用SALL（SAM生产Salinospora tropica）与C-甲基NOVO（链霉菌spheroides）使一套甲基化和乙基香豆素产物的合成，这表现为标记13 CH 3，13 CD 3及CD 3组从它们相应的SAM类似物。
• Cfr and RlmN Contain a Single [4Fe-4S] Cluster, which Directs Two Distinct Reactivities for <i>S</i>-Adenosylmethionine: Methyl Transfer by S_N2 Displacement and Radical Generation
  作者：Tyler L. Grove、Matthew I. Radle、Carsten Krebs、Squire J. Booker

  DOI：10.1021/ja207327v

  日期：2011.12.14

  The radical SAM (RS) proteins RlmN and Cfr catalyze methylation of carbons 2 and 8, respectively, of adenosine 2503 in 235 rRNA. Both reactions are similar in scope, entailing the synthesis of a methyl group partially derived from S-adenosylmethionine (SAM) onto electrophilic sp(2)-hybridized carbon atoms via the intermediacy of a protein S-methylcysteinyl (mCys) residue. Both proteins contain five conserved Cys residues, each required for turnover. Three cysteines lie in a canonical RS CxxxCxxC motif and coordinate a [4Fe-4S]-cluster cofactor; the remaining two are at opposite ends of the polypeptide. Here we show that each protein contains only the one "radical SAM" [4Fe-4S] cluster and the two remaining conserved cysteines do not coordinate additional iron-containing species. In addition, we show that, while wild-type RlmN bears the C355 mCys residue in its as-isolated state, RlmN that is either engineered to lack the [4Fe-4S] duster by substitution of the coordinating cysteines or isolated from Escherichia coli cultured under iron-limiting conditions does not bear a C355 mCys residue. Reconstitution of the [4Fe-4S] cluster on wild-type apo RlmN followed by addition of SAM results in rapid production of S-adenosylhomocysteine (SAH) and the mCys residue, while treatment of apo RlmN with SAM affords no observable reaction. These results indicate that in Cfr and RlmN, SAM bound to the unique iron of the [4Fe-4S] duster displays two reactivities. It serves to methylate C355 of RlmN (C338 of Cfr), or to generate the 5'-deoxyadenosyl 5'-radical, required for substrate-dependent methyl synthase activity.