3,22-dioxochol-4-en-24-oyl-CoA(4-)

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 3,22-dioxochol-4-en-24-oyl-CoA(4-)
• 英文别名: [(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-2-[[[[(3R)-4-[[3-[2-[(4S)-4-[(8S,9S,10R,13S,14S,17R)-10,13-dimethyl-3-oxo-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl]-3-oxopentanoyl]sulfanylethylamino]-3-oxopropyl]amino]-3-hydroxy-2,2-dimethyl-4-oxobutoxy]-oxidophosphoryl]oxy-oxidophosphoryl]oxymethyl]-4-hydroxyoxolan-3-yl] phosphate
• 化学式: C45H64N7O19P3S-4
• 分子量: 1132.0
• InChiKey: MUOUYOUSQGFFIP-GDRSPGQTSA-J

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  75
• 可旋转键数：
  23
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  434
• 氢给体数：
  5
• 氢受体数：
  24

反应信息

• 作为产物：
  描述：

  3-oxo-23,24-bisnorchol-4-en-22-oyl-CoA(4-) 、 (2R)-N-[3-(2-acetylsulfanylethylimino)-3-oxidopropyl]-4-[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonatooxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]oxy-2-hydroxy-3,3-dimethylbutanimidate 生成 3,22-dioxochol-4-en-24-oyl-CoA(4-) 、 coenzyme A
  参考文献：
  名称：

  FadA5 a Thiolase from Mycobacterium tuberculosis : A Steroid-Binding Pocket Reveals the Potential for Drug Development against Tuberculosis

  摘要：

  With the exception of HIV, tuberculosis (TB) is the leading cause of mortality among infectious diseases. The urgent need to develop new antitubercular drugs is apparent due to the increasing number of drug-resistant Mycobacterium tuberculosis (Mtb) strains. Proteins involved in cholesterol import and metabolism have recently been discovered as potent targets against TB. FadA5, a thiolase from Mtb, is catalyzing the last step of the beta-oxidation reaction of the cholesterol side-chain degradation under release of critical metabolites and was shown to be of importance during the chronic stage of TB infections. To gain structural and mechanistic insight on FadA5, we characterized the enzyme in different stages of the cleavage reaction and with a steroid bound to the binding pocket. Structural comparisons to human thiolases revealed that it should be possible to target FadA5 specifically, and the steroid-bound structure provides a solid basis for the development of inhibitors against FadA5.

  DOI：

  10.1016/j.str.2014.10.010

文献信息

• FadA5 a Thiolase from Mycobacterium tuberculosis : A Steroid-Binding Pocket Reveals the Potential for Drug Development against Tuberculosis
  作者：Christin M. Schaefer、Rui Lu、Natasha M. Nesbitt、Johannes Schiebel、Nicole S. Sampson、Caroline Kisker

  DOI：10.1016/j.str.2014.10.010

  日期：2015.1

  With the exception of HIV, tuberculosis (TB) is the leading cause of mortality among infectious diseases. The urgent need to develop new antitubercular drugs is apparent due to the increasing number of drug-resistant Mycobacterium tuberculosis (Mtb) strains. Proteins involved in cholesterol import and metabolism have recently been discovered as potent targets against TB. FadA5, a thiolase from Mtb, is catalyzing the last step of the beta-oxidation reaction of the cholesterol side-chain degradation under release of critical metabolites and was shown to be of importance during the chronic stage of TB infections. To gain structural and mechanistic insight on FadA5, we characterized the enzyme in different stages of the cleavage reaction and with a steroid bound to the binding pocket. Structural comparisons to human thiolases revealed that it should be possible to target FadA5 specifically, and the steroid-bound structure provides a solid basis for the development of inhibitors against FadA5.