cADPR

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: cADPR
• 英文别名: (2R,3R,4S,5R,13R,14S,15R,16R)-24-amino-10-hydroxy-8-oxido-8,10-dioxo-7,9,11,25,26-pentaoxa-17,19,22-triaza-1-azonia-8lambda5,10lambda5-diphosphapentacyclo[18.3.1.12,5.113,16.017,21]hexacosa-1(24),18,20,22-tetraene-3,4,14,15-tetrol；(2R,3R,4S,5R,13R,14S,15R,16R)-24-amino-10-hydroxy-8-oxido-8,10-dioxo-7,9,11,25,26-pentaoxa-17,19,22-triaza-1-azonia-8λ5,10λ5-diphosphapentacyclo[18.3.1.12,5.113,16.017,21]hexacosa-1(24),18,20,22-tetraene-3,4,14,15-tetrol
• 化学式: C₁₅H₂₁N₅O₁₃P₂
• 分子量: 541.305
• InChiKey: RSEFDAKYCYLNIE-KEOHHSTQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.8
• 重原子数：
  35
• 可旋转键数：
  0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  265
• 氢给体数：
  6
• 氢受体数：
  16

反应信息

• 作为产物：
  描述：

  β-烟酰胺腺嘌呤二核苷酸 在 Schistosoma mansoni NAD⁺ catabolizing enzyme H₁₀₃A 作用下， 生成 cADPR 、 ADP ribose
  参考文献：
  名称：

  Schistosoma mansoni NAD+ catabolizing enzyme: Identification of key residues in catalysis

  摘要：

  Schistosoma mansoni NAD(+) catabolizing enzyme (SmNACE), a distant homolog of mammalian CD38, shows significant structural and functional analogy to the members of the CD38/ADP-ribosyl cyclase family. The hallmark of SmNACE is the lack of ADP-ribosyl cyclase activity that might be ascribed to subtle changes in its active site. To better characterize the residues of the active site we determined the kinetic parameters of nine mutants encompassing three acidic residues: (i) the putative catalytic residue Glu202 and (ii) two acidic residues within the 'signature' region (the conserved Glu124 and the downstream Asp133), (iii) Ser169, a strictly conserved polar residue and (iv) two aromatic residues (His103 and Trp165). We established the very important role of Glu202 and of the hydrophobic domains overwhelmingly in the efficiency of the nicotinamide-ribosyl bond cleavage step. We also demonstrated that in sharp contrast with mammalian CD38, the 'signature' Glu124 is as critical as Glu202 for catalysis by the parasite enzyme. The different environments of the two Glu residues in the crystal structure of CD38 and in the homology model of SmNACE could explain such functional discrepancies. Mutagenesis data and 3D structures also indicated the importance of aromatic residues, especially His103, in the stabilization of the reaction intermediate as well as in the selection of its conformation suitable for cyclization to cyclic ADP-ribose. Finally, we showed that inhibition of SmNACE by the natural product cyanidin requires the integrity of Glu202 and Glu124, but not of His103 and Trp165, hence suggesting different recognition modes for substrate and inhibitor. (C) 2013 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.bbapap.2013.09.002