5-Phosphoribosyl-1-(beta-methylene) pyrophosphate | 95188-97-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-Phosphoribosyl-1-(beta-methylene) pyrophosphate
• 英文别名: [[(2R,3R,4S,5R)-3,4-dihydroxy-5-(phosphonooxymethyl)oxolan-2-yl]oxy-hydroxyphosphoryl]methylphosphonic acid
• CAS: 95188-97-9
• 化学式: C₆H₁₅O₁₃P₃
• 分子量: 388.099
• InChiKey: JFMKBQDEISBIPL-KVTDHHQDSA-N

物化性质

• 沸点：
  823.6±75.0 °C(Predicted)
• 密度：
  2.03±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -6
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  221
• 氢给体数：
  7
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  5-Phosphoribosyl-1-(beta-methylene) pyrophosphate 、 次黄嘌呤 在 Leishmania donovani adenine phosphoribosyltransferase 、 sodium fluoride 、 magnesium chloride 作用下， 反应 1.0h， 生成 5’-肌苷酸
  参考文献：
  名称：

  Amplification of Adenine Phosphoribosyltransferase Suppresses the Conditionally Lethal Growth and Virulence Phenotype of Leishmania donovani Mutants Lacking Both Hypoxanthine-guanine and Xanthine Phosphoribosyltransferases

  摘要：

  Leishmania donovani cannot synthesize purines de novo and obligatorily scavenge purines from the host. Previously, we described a conditional lethal Delta hgprt/Delta xprt mutant of L. donovani (Boitz, J. M., and Ullman, B. (2006) J. Biol. Chem. 281, 16084-16089) that establishes that L. donovani salvages purines primarily through hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and xanthine phosphoribosyltransferase (XPRT). Unlike wild type L. donovani, the Delta hgprt/Delta xprt knockout cannot grow on 6-oxypurines and displays an absolute requirement for adenine or adenosine and 2'-deoxycoformycin, an inhibitor of parasite adenine aminohydrolase activity. Here, we demonstrate that the ability of Delta hgprt/Delta xprt parasites to infect mice was profoundly compromised. Surprisingly, mutant parasites that survived the initial passage through mice partially regained their virulence properties, exhibiting a >10-fold increase in parasite burden in a subsequent mouse infection. To dissect the mechanism by which Delta hgprt/Delta xprt parasites persisted in vivo, suppressor strains that had regained their capacity to grow under restrictive conditions were cloned from cultured Delta hgprt/Delta xprt parasites. The ability of these suppressor clones to grow in and metabolize 6-oxypurines could be ascribed to a marked amplification and overexpression of the adenine phosphoribosyltransferase (APRT) gene. Moreover, transfection of Delta hgprt/Delta xprt cells with an APRT episome recapitulated the suppressor phenotype in vitro and enabled growth on 6-oxypurines. Biochemical studies further showed that hypoxanthine, unexpectedly, was an inefficient substrate for APRT, evidence that could account for the ability of the suppressors to metabolize hypoxanthine. Subsequent analysis implied that APRT amplification was also a potential contributory mechanism by which Delta hgprt/Delta xprt parasites displayed persistence and increased virulence in mice.

  DOI：

  10.1074/jbc.m110.125393

文献信息

• Amplification of Adenine Phosphoribosyltransferase Suppresses the Conditionally Lethal Growth and Virulence Phenotype of Leishmania donovani Mutants Lacking Both Hypoxanthine-guanine and Xanthine Phosphoribosyltransferases
  作者：Jan M. Boitz、Buddy Ullman

  DOI：10.1074/jbc.m110.125393

  日期：2010.6

  Leishmania donovani cannot synthesize purines de novo and obligatorily scavenge purines from the host. Previously, we described a conditional lethal Delta hgprt/Delta xprt mutant of L. donovani (Boitz, J. M., and Ullman, B. (2006) J. Biol. Chem. 281, 16084-16089) that establishes that L. donovani salvages purines primarily through hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and xanthine phosphoribosyltransferase (XPRT). Unlike wild type L. donovani, the Delta hgprt/Delta xprt knockout cannot grow on 6-oxypurines and displays an absolute requirement for adenine or adenosine and 2'-deoxycoformycin, an inhibitor of parasite adenine aminohydrolase activity. Here, we demonstrate that the ability of Delta hgprt/Delta xprt parasites to infect mice was profoundly compromised. Surprisingly, mutant parasites that survived the initial passage through mice partially regained their virulence properties, exhibiting a >10-fold increase in parasite burden in a subsequent mouse infection. To dissect the mechanism by which Delta hgprt/Delta xprt parasites persisted in vivo, suppressor strains that had regained their capacity to grow under restrictive conditions were cloned from cultured Delta hgprt/Delta xprt parasites. The ability of these suppressor clones to grow in and metabolize 6-oxypurines could be ascribed to a marked amplification and overexpression of the adenine phosphoribosyltransferase (APRT) gene. Moreover, transfection of Delta hgprt/Delta xprt cells with an APRT episome recapitulated the suppressor phenotype in vitro and enabled growth on 6-oxypurines. Biochemical studies further showed that hypoxanthine, unexpectedly, was an inefficient substrate for APRT, evidence that could account for the ability of the suppressors to metabolize hypoxanthine. Subsequent analysis implied that APRT amplification was also a potential contributory mechanism by which Delta hgprt/Delta xprt parasites displayed persistence and increased virulence in mice.