3,17-dihydroxy-9,10-secoandrost-1,3,5(10)-trien-9-one | 848360-74-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 3,17-dihydroxy-9,10-secoandrost-1,3,5(10)-trien-9-one
• 英文别名: 3,17-DHSA；(3aS,4S,7aS)-1-hydroxy-4-[2-(5-hydroxy-2-methylphenyl)ethyl]-7a-methyl-2,3,3a,4,6,7-hexahydro-1H-inden-5-one
• CAS: 848360-74-7
• 化学式: C₁₉H₂₆O₃
• 分子量: 302.414
• InChiKey: KNUPPCXYOSQLJL-TZEXOCCPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3,17-dihydroxy-9,10-secoandrost-1,3,5(10)-trien-9-one 在 recombinant Mycobacterium tuberculosis 3-hydroxy-9,10-seconandrost-1,3,5⁽¹⁰⁾-triene-9,17-dione 4-hydroxylase 、 氧气 、 2,6-蒽二酚 、 还原型辅酶Ⅰ 作用下， 以 水 为溶剂， 生成 3,4,17-trihydroxy-9,10-secoandrosta-1,3,5(10)-triene-9-one
  参考文献：
  名称：

  A Flavin-dependent Monooxygenase from Mycobacterium tuberculosis Involved in Cholesterol Catabolism

  摘要：

  Mycobacterium tuberculosis (Mtb) and Rhodococcus jostii RHA1 have similar cholesterol catabolic pathways. This pathway contributes to the pathogenicity of Mtb. The hsaAB cholesterol catabolic genes have been predicted to encode the oxygenase and reductase, respectively, of a flavin-dependent mono-oxygenase that hydroxylates 3-hydroxy-9,10-seconandrost-1,3,5(10)-triene-9,17- dione (3-HSA) to a catechol. An hsaA deletion mutant of RHA1 did not grow on cholesterol but transformed the latter to 3-HSA and related metabolites in which each of the two keto groups was reduced: 3,9-dihydroxy-9,10-seconandrost-1,3,5(10)-triene- 17-one (3,9-DHSA) and 3,17-dihydroxy-9,10-seconandrost-1,3,5( 10)-triene-9-one (3,17-DHSA). Purified 3-hydroxy-9,10- seconandrost-1,3,5(10)-triene-9,17-dione 4-hydroxylase (HsaAB) from Mtb had higher specificity for 3-HSA than for 3,17-DHSA (apparent k(cat)/K-m =1000 +/- 100 M-1 s(-1) versus 700 +/- 100 M-1 s(-1)). However, 3,9-DHSA was a poorer substrate than 3-hydroxybiphenyl (apparent k(cat)/K-m = 80 +/- 40 M-1 s(-1)). In the presence of 3-HSA the K-mapp for O-2 was 100 +/- 10 mu M. The crystal structure of HsaA to 2.5-angstrom resolution revealed that the enzyme has the same fold, flavin-binding site, and catalytic residues as p-hydroxyphenyl acetate hydroxylase. However, HsaA has a much larger phenol-binding site, consistent with the enzyme's substrate specificity. In addition, a second crystal form of HsaA revealed that a C-terminal flap (Val(367)-Val(394)) could adopt two conformations differing by a rigid body rotation of 25 degrees around Arg(366). This rotation appears to gate the likely flavin entrance to the active site. In docking studies with 3-HSA and flavin, the closed conformation provided a rationale for the enzyme's substrate specificity. Overall, the structural and functional data establish the physiological role of HsaAB and provide a basis to further investigate an important class of monooxygenases as well as the bacterial catabolism of steroids.

  DOI：

  10.1074/jbc.m109.099028