2''-O-glutaryl-ADP-D-ribose(3-)

• 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: 2''-O-glutaryl-ADP-D-ribose(3-)
• 英文别名: 5-[(3R,4R,5R)-5-[[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl]oxy-oxidophosphoryl]oxymethyl]-2,4-dihydroxyoxolan-3-yl]oxy-5-oxopentanoate
• 化学式: C20H26N5O17P2-3
• 分子量: 670.4
• InChiKey: YKONEZRCCFZUGL-GCGJIVQHSA-K

计算性质

• 辛醇/水分配系数(LogP)：
  -5.3
• 重原子数：
  44
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  343
• 氢给体数：
  5
• 氢受体数：
  21

反应信息

• 作为产物：
  描述：

  水 、 N⁶-glutaryl-L-lysine residue 、 nicotinamide adenine dinucleotide 生成 2''-O-glutaryl-ADP-D-ribose(3-) 、 L-lysine residue 、 烟酰胺
  参考文献：
  名称：

  Lysine Glutarylation Is a Protein Posttranslational Modification Regulated by SIRT5

  摘要：

  We report the identification and characterization of a five-carbon protein posttranslational modification (PTM) called lysine glutarylation (K-glu). This protein modification was detected by immunoblot and mass spectrometry (MS), and then comprehensively validated by chemical and biochemical methods. We demonstrated that the previously annotated deacetylase, sirtuin 5 (SIRT5), is a lysine deglutarylase. Proteome-wide analysis identified 683 Kglu sites in 191 proteins and showed that Kglu is highly enriched on metabolic enzymes and mitochondrial proteins. We validated carbamoyl phosphate synthase 1 (CPS1), the rate-limiting enzyme in urea cycle, as a glutarylated protein and demonstrated that CPS1 is targeted by SIRT5 for deglutarylation. We further showed that glutarylation suppresses CPS1 enzymatic activity in cell lines, mice, and a model of glutaric acidemia type I disease, the last of which has elevated glutaric acid and glutaryl-CoA. This study expands the landscape of lysine acyl modifications and increases our understanding of the deacylase SIRT5.

  DOI：

  10.1016/j.cmet.2014.03.014