3OAADPr

• 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: 3OAADPr
• 英文别名: [[(2R,3S,4R)-3-acetyloxy-4,5-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: HNHCIVXQBMBKPQ-YDKGJHSESA-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：

  3OAADPr 、 水 生成 乙酸盐 、 ADP-ribose 、 氢(+1)阳离子
  参考文献：
  名称：

  MacroD1 是一种定位于线粒体的混杂 ADP-核糖基水解酶。

  摘要：

  MacroD1 是一种含有宏域的蛋白质，它对几个 ADP-核糖加合物具有单 ADP-核糖水解酶的酶活性。MacroD1 表达的失调已被证明与几种癌症的发病机制有关。迄今为止，MacroD1 的生理功能和亚细胞定位尚不清楚。以前的研究描述了 MacroD1 的核和细胞质功能。然而，在这项研究中，我们表明内源性 MacroD1 蛋白在线粒体中高度富集。我们还表明 MacroD1 在人和小鼠骨骼肌中高度表达。此外，我们表明 MacroD1 可以在体外有效地从 5' 和 3'-磷酸化双链 DNA 加合物中去除 ADP-核糖。总体，我们已经证明 MacroD1 是一种具有混杂酶活性的线粒体蛋白，可以靶向 ADP 核糖化磷酸化双链 DNA 末端的酯键。这些发现对 MacroD1 和 ADP 核糖基化在体内线粒体功能和 DNA 损伤的调节中具有令人兴奋的意义。

  DOI：

  10.3389/fmicb.2018.00020

文献信息

• Identification of Macrodomain Proteins as Novel O-Acetyl-ADP-ribose Deacetylases
  作者：Dawei Chen、Melanie Vollmar、Marianna N. Rossi、Claire Phillips、Rolf Kraehenbuehl、Dea Slade、Pawan V. Mehrotra、Frank von Delft、Susan K. Crosthwaite、Opher Gileadi、John M. Denu、Ivan Ahel

  DOI：10.1074/jbc.m110.206771

  日期：2011.4

  Sirtuins are a family of protein lysine deacetylases, which regulate gene silencing, metabolism, life span, and chromatin structure. Sirtuins utilize NAD(+) to deacetylate proteins, yielding O-acetyl-ADP-ribose (OAADPr) as a reaction product. The macrodomain is a ubiquitous protein module known to bind ADP-ribose derivatives, which diverged through evolution to support many different protein functions and pathways. The observation that some sirtuins and macrodomains are physically linked as fusion proteins or genetically coupled through the same operon, provided a clue that their functions might be connected. Indeed, here we demonstrate that the product of the sirtuin reaction OAADPr is a substrate for several related macrodomain proteins: human MacroD1, human MacroD2, Escherichia coli YmdB, and the sirtuin-linked MacroD-like protein from Staphylococcus aureus. In addition, we show that the cell extracts derived from MacroD-deficient Neurospora crassa strain exhibit a major reduction in the ability to hydrolyze OAADPr. Our data support a novel function of macrodomains as OAADPr deacetylases and potential in vivo regulators of cellular OAADPr produced by NAD(+)-dependent deacetylation.
• Structural insights into the mechanism of Escherichia coli YmdB: A 2′- O -acetyl-ADP-ribose deacetylase
  作者：Weichang Zhang、Chengliang Wang、Yang Song、Chen Shao、Xuan Zhang、Jianye Zang

  DOI：10.1016/j.jsb.2015.10.010

  日期：2015.12

  The Escherichia coli protein YmdB belongs to the macrodomain protein family, which can bind ADP-ribose (ADPr) and its derivatives. Recently, YmdB was reported to be capable of deacetylating O-acetyl-ADP-ribose (0AADPr) to yield ADPr and free acetate. To study the substrate specificity and catalytic mechanism, the crystal structures of E. coli YmdB in complex with ADPr, double mutant N25AD35A complexed with 2'-OAADPr, and Y126A/ADPr complex were solved at 1.8 angstrom, 2.8 angstrom and 3.0 angstrom resolution, respectively. Structural and biochemical studies reveal that YmdB has substrate specificity against 2'-OAADPr. The conserved residues Asn25 and Asp35 are crucial for catalytic activity, and an active water molecule is proposed as the nucleophile to attack the acetyl group of 2'-OAADPr. Our findings indicate that the conserved phenyl group of Tyr126 plays a crucial role in catalytic activity by stabilizing the right orientation of distal ribose and that Gly32 may be important for activity by interacting with the acetyl group of 2'-OAADPr. Based on these observations, a model of YmdB in complex with 2'-OAADPr was made to illustrate the proposed catalytic mechanism of YmdB. (C) 2015 Elsevier Inc. All rights reserved.