...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The N-terminal domain of mammalian soluble epoxide hydrolase is a phosphatase.
【24h】

The N-terminal domain of mammalian soluble epoxide hydrolase is a phosphatase.

机译：哺乳动物可溶性环氧化物水解酶的N-末端结构域是磷酸酶。

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 mammalian soluble epoxide hydrolase (sEH) is an enzyme with multiple functions, being implicated in detoxification of xenobiotic epoxides as well as in regulation of physiological processes such as blood pressure. The enzyme is a homodimer, in which each subunit is composed of two domains. The 35-kDa C-terminal domain has an alpha/beta hydrolase fold and harbors the catalytic center for the EH activity. The 25-kDa N-terminal domain has a different alpha/beta fold and belongs to the haloacid dehalogenase superfamily of enzymes. The catalytic properties of the enzyme reported so far can all be explained by the action of the C-terminal domain alone. The function of the N-terminal domain, other than in structural stabilization of the dimer, has therefore remained unclear. By structural comparison of this domain to other haloacid dehalogenase family members, we identified a putative active site containing all necessary components for phosphatase activity. Subsequently, we found rat sEH hydrolyzed 4-nitrophenyl phosphate with a rate constant of 0.8 s(-1) and a K(m) of 0.24 mM. Recombinant human sEH lacking the C-terminal domain also displayed phosphatase activity. Presence of a phosphatase substrate did not affect epoxide turnover nor did epoxides affect dephosphorylation by the intact enzyme, indicating both catalytic sites act independently. The enzyme was unable to hydrolyze 4-nitrophenyl sulfate, suggesting its role in xenobiotic metabolism does not extend beyond phosphates. Thus, we propose this domain participates instead in the regulation of the physiological functions associated with sEH.
机译：哺乳动物可溶性环氧化物水解酶（sEH）是一种具有多种功能的酶，与异种环氧化物的解毒以及生理过程（例如血压）的调节有关。该酶是同型二聚体，其中每个亚基由两个结构域组成。 35 kDa的C末端结构域具有α/β水解酶折叠，并具有EH活性的催化中心。 25 kDa N末端结构域具有不同的alpha / beta折叠，并且属于酶的卤酸脱卤酶超家族。迄今为止报道的酶的催化性质全部可以通过单独的C-末端结构域的作用来解释。因此，除二聚体的结构稳定以外，N末端结构域的功能仍然不清楚。通过对该结构域与其他卤代酸脱卤酶家族成员的结构比较，我们确定了一个推定的活性位点，其中包含磷酸酶活性的所有必需成分。随后，我们发现大鼠sEH水解了4-硝基苯基磷酸酯，其速率常数为0.8 s（-1），K（m）为0.24 mM。缺乏C末端结构域的重组人sEH也显示出磷酸酶活性。磷酸酶底物的存在既不影响环氧化物的转化，也不影响环氧化物通过完整酶的去磷酸化，表明两个催化位点均独立起作用。该酶无法水解4-硝基苯基硫酸盐，表明其在异生物代谢中的作用并不超出磷酸盐。因此，我们建议该域参与与sEH相关的生理功能的调节。

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