...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Endocrine Research >Molecular modeling of the hamster adrenal P450C17.
【24h】

Molecular modeling of the hamster adrenal P450C17.

机译：仓鼠肾上腺P450C17的分子模型。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The cytochrome P450C17 (C17) is the steroidogenic enzyme responsible for the conversion of pregnenolone and progesterone to dehydroepiandrosterone (DHEA) and delta4-androstenedione (AD) respectively. This conversion is achieved by two enzymatic activities, 17alpha-hydroxylase and 17,20-lyase, located at the same active site. In man, the adrenal C17 basically only produces DHEA. We have shown that the hamster adrenal C17 produces DHEA as well as AD. Moreover, the hamster like man produces cortisol as its major glucocorticoid. We can thus compare the hamster and human adrenal C17, and use their differences in order to elaborate a strategy for structure-function studies. We have thus engineered hamster adrenal C17 mutants which possess modified enzymatic activities. We also proceeded to elaborate a three-dimensional model of the hamster C17 to visualise the structural impact of these mutations. This model demonstrates that the mutations created are not localised at the active site, but rather in surrounding regions. These could affect the conformation of the active site, in turn, modulating the 17alpha-hydroxylase and 17,20-lyase activities. For example, the mutation T202N is located next to Val 482 and Val 483 which compose the roof of the active site. This mutation decreased both 17alpha-hydroxylase and 17,20-lyase activities, indicating the importance of the roof of the active site for general functionality of the C17.
机译：细胞色素P450C17（C17）是类固醇生成酶，负责将孕烯醇酮和孕酮分别转化为脱氢表雄酮（DHEA）和δ4-雄烯二酮（AD）。这种转化是通过位于同一活性位点的两种酶促活性，即17α-羟化酶和17,20-裂合酶来实现的。在人类中，肾上腺C17基本上只产生DHEA。我们已经证明仓鼠肾上腺C17产生DHEA和AD。此外，仓鼠像人一样产生皮质醇作为其主要的糖皮质激素。因此，我们可以比较仓鼠和人类肾上腺C17，并利用它们的差异来阐述结构功能研究的策略。因此，我们设计了具有修饰的酶活性的仓鼠肾上腺C17突变体。我们还着手阐述了仓鼠C17的三维模型，以可视化这些突变的结构影响。该模型表明，产生的突变并不位于活性位点，而是位于周围区域。这些可能会影响活性位点的构象，进而调节17α-羟化酶和17,20-裂合酶的活性。例如，突变T202N位于构成活性位点屋顶的Val 482和Val 483旁边。这种突变降低了17α-羟化酶和17,20-裂合酶的活性，表明活性位点的顶部对于C17的一般功能很重要。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号