3-hydroxyanthraniloyl adenosine monophosphate | 88609-71-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 英文名称: 3-hydroxyanthraniloyl adenosine monophosphate
• CAS: 88609-71-6
• 化学式: C₁₇H₁₉N₆O₉P
• 分子量: 482.346
• InChiKey: OXKYRLPWERFKRY-RVXWVPLUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.71
• 重原子数：
  33.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  238.39
• 氢给体数：
  6.0
• 氢受体数：
  14.0

反应信息

• 作为产物：
  描述：

  γ-(18)O4-ATP 、 3-羟基-2-氨基苯甲酸 在 二磷酸酯 、 ORF₂₁, C-terminal His₆-tagged 、 甘油 、 magnesium chloride 、 Cleland's reagent 作用下， 反应 0.5h， 生成 3-hydroxyanthraniloyl adenosine monophosphate
  参考文献：
  名称：

  Adenylation Enzyme Characterization Using γ -18O4-ATP Pyrophosphate Exchange

  摘要：

  We present here a rapid, highly sensitive nonradioactive assay for adenylation enzyme selectivity determination and characterization. This method measures the isotopic back exchange of unlabeled pyrophosphate into gamma-O-18(4)-labeled ATP via matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS), electrospray ionization liquid chromatography MS, or electrospray ionization liquid chromatography-tandem MS and is demonstrated for both nonribosomal (TycA, ValA) and ribosomal synthetases (TrpRS, LysRS) of known specificity. This low-volume (6 mu l) method detects as little as 0.01% (600 fmol) exchange, comparable in sensitivity to previously reported radioactive assays and readily adaptable to kinetics measurements and high throughput analysis of a wide spectrum of synthetases. Finally, a previously uncharacterized A-T didomain from anthramycin biosynthesis in the thermophile S. refuinius was demonstrated to selectively activate 4-methyl-3-hydroxyanthranilic acid at 47 degrees C, providing biochemical evidence for a new aromatic beta-amino acid activating adenylation domain and the first functional analysis of the anthramycin biosynthetic gene cluster.

  DOI：

  10.1016/j.chembiol.2009.04.007

文献信息

• Biosynthesis, Mechanism of Action, and Inhibition of the Enterotoxin Tilimycin Produced by the Opportunistic Pathogen <i>Klebsiella oxytoca</i>
  作者：Evan M. Alexander、Dale F. Kreitler、Valeria Guidolin、Alexander K. Hurben、Eric Drake、Peter W. Villalta、Silvia Balbo、Andrew M. Gulick、Courtney C. Aldrich

  DOI：10.1021/acsinfecdis.0c00326

  日期：2020.7.10

  Tilimycin is an enterotoxin produced by the opportunistic pathogen Klebsiella oxytoca that causes antibiotic-associated hemorrhagic colitis (AAHC). This pyrrolobenzodiazepine (PBD) natural product is synthesized by a bimodular nonribosomal peptide synthetase (NRPS) pathway composed of three proteins: NpsA, ThdA, and NpsB. We describe the functional and structural characterization of the fully reconstituted NRPS system and report the steady-state kinetic analysis of all natural substrates and cofactors as well as the structural characterization of both NpsA and ThdA. The mechanism of action of tilimycin was confirmed using DNA adductomics techniques through the detection of putative N-2 guanine alkylation after tilimycin exposure to eukaryotic cells, providing the first structural characterization of a PBD-DNA adduct formed in cells. Finally, we report the rational design of small-molecule inhibitors that block tilimycin biosynthesis in whole cell K. oxytoca (IC₅₀ = 29 ± 4 μM) through the inhibition of NpsA (K_D = 29 ± 4 nM).