acetyl-ADP-ribose

• 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: acetyl-ADP-ribose
• 英文别名: [[(2R,3S,4R,5R)-5-acetyloxy-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl] [(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate
• 化学式: C17H23N5O15P2-2
• 分子量: 599.3
• InChiKey: IJOUKWCBVUMMCR-DLFWLGJNSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  -5.7
• 重原子数：
  39
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  303
• 氢给体数：
  5
• 氢受体数：
  19

反应信息

• 作为反应物：
  描述：

  acetyl-ADP-ribose 、 水 生成 乙酸盐 、 ADP-ribose 、 氢(+1)阳离子
  参考文献：
  名称：

  Hydrolysis of O-Acetyl-ADP-ribose Isomers by ADP-ribosylhydrolase 3

  摘要：

  O-Acetyl-ADP-ribose (OAADPr), produced by the Sir2-catalyzed NAD(+)-dependent histone/protein deacetylase reaction, regulates diverse biological processes. Interconversion between two OAADPr isomers with acetyl attached to the C-2 '' and C-3 '' hydroxyl of ADP-ribose (ADPr) is rapid. We reported earlier that ADP-ribosylhydrolase 3 (ARH3), one of three ARH proteins sharing structural similarities, hydrolyzed OAADPr to ADPr and acetate, and poly(ADPr) to ADPr monomers. ARH1 also hydrolyzed OAADPr and poly(ADPr) as well as ADP-ribose-arginine, with arginine in alpha-anomeric linkage to C-1 '' of ADP-ribose. Because both ARH3- and ARH1-catalyzed reactions involve nucleophilic attacks at the C-1 '' position, it was perplexing that the ARH3 catalytic site would cleave OAADPr at either the 2 ''- or 3 ''-position, and we postulated the existence of a third isomer, 1 ''-OAADPr, in equilibrium with 2 ''- and 3 ''-isomers. A third isomer, consistent with 1 ''-OAADPr, was identified at pH 9.0. Further, ARH3 OAADPr hydrolase activity was greater at pH 9.0 than at neutral pH where 3 ''-OAADPr predominated. Consistent with our hypothesis, IC50 values for ARH3 inhibition by 2 ''- and 3 ''-N-acetyl-ADPr analogs of OAADPr were significantly higher than that for ADPr. ARH1 also hydrolyzed OAADPr more rapidly at alkaline pH, but cleavage of ADP-ribose-arginine was faster at neutral pH than pH 9.0. ARH3-catalyzed hydrolysis of OAADPr in H-2 O-18 resulted in incorporation of one O-18 into ADP-ribose by mass spectrometric analysis, consistent with cleavage at the C-1 '' position. Together, these data suggest that ARH family members, ARH1 and ARH3, catalyze hydrolysis of the 1 ''-O linkage in their structurally diverse substrates.

  DOI：

  10.1074/jbc.m111.237636

文献信息

• Hydrolysis of O-Acetyl-ADP-ribose Isomers by ADP-ribosylhydrolase 3
  作者：Atsushi Kasamatsu、Motoyuki Nakao、Brian C. Smith、Lindsay R. Comstock、Tohru Ono、Jiro Kato、John M. Denu、Joel Moss

  DOI：10.1074/jbc.m111.237636

  日期：2011.6

  O-Acetyl-ADP-ribose (OAADPr), produced by the Sir2-catalyzed NAD(+)-dependent histone/protein deacetylase reaction, regulates diverse biological processes. Interconversion between two OAADPr isomers with acetyl attached to the C-2 '' and C-3 '' hydroxyl of ADP-ribose (ADPr) is rapid. We reported earlier that ADP-ribosylhydrolase 3 (ARH3), one of three ARH proteins sharing structural similarities, hydrolyzed OAADPr to ADPr and acetate, and poly(ADPr) to ADPr monomers. ARH1 also hydrolyzed OAADPr and poly(ADPr) as well as ADP-ribose-arginine, with arginine in alpha-anomeric linkage to C-1 '' of ADP-ribose. Because both ARH3- and ARH1-catalyzed reactions involve nucleophilic attacks at the C-1 '' position, it was perplexing that the ARH3 catalytic site would cleave OAADPr at either the 2 ''- or 3 ''-position, and we postulated the existence of a third isomer, 1 ''-OAADPr, in equilibrium with 2 ''- and 3 ''-isomers. A third isomer, consistent with 1 ''-OAADPr, was identified at pH 9.0. Further, ARH3 OAADPr hydrolase activity was greater at pH 9.0 than at neutral pH where 3 ''-OAADPr predominated. Consistent with our hypothesis, IC50 values for ARH3 inhibition by 2 ''- and 3 ''-N-acetyl-ADPr analogs of OAADPr were significantly higher than that for ADPr. ARH1 also hydrolyzed OAADPr more rapidly at alkaline pH, but cleavage of ADP-ribose-arginine was faster at neutral pH than pH 9.0. ARH3-catalyzed hydrolysis of OAADPr in H-2 O-18 resulted in incorporation of one O-18 into ADP-ribose by mass spectrometric analysis, consistent with cleavage at the C-1 '' position. Together, these data suggest that ARH family members, ARH1 and ARH3, catalyze hydrolysis of the 1 ''-O linkage in their structurally diverse substrates.