...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The FEBS journal >Evidence for the slow reaction of hypoxia-inducible factor prolyl hydroxylase 2 with oxygen.
【24h】

Evidence for the slow reaction of hypoxia-inducible factor prolyl hydroxylase 2 with oxygen.

机译：缺氧诱导因子脯氨酰羟化酶2与氧气反应缓慢的证据。

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 response of animals to hypoxia is mediated by the hypoxia-inducible transcription factor. Human hypoxia-inducible factor is regulated by four Fe(II)- and 2-oxoglutarate-dependent oxygenases: prolyl hydroxylase domain enzymes 1-3 catalyse hydroxylation of two prolyl-residues in hypoxia-inducible factor, triggering its degradation by the proteasome. Factor inhibiting hypoxia-inducible factor catalyses the hydroxylation of an asparagine-residue in hypoxia-inducible factor, inhibiting its transcriptional activity. Collectively, the hypoxia-inducible factor hydroxylases negatively regulate hypoxia-inducible factor in response to increasing oxygen concentration. Prolyl hydroxylase domain 2 is the most important oxygen sensor in human cells; however, the underlying kinetic basis of the oxygen-sensing function of prolyl hydroxylase domain 2 is unclear. We report analyses of the reaction of prolyl hydroxylase domain 2 with oxygen. Chemical quench/MS experiments demonstrate that reaction of a complex of prolyl hydroxylase domain 2, Fe(II), 2-oxoglutarate and the C-terminal oxygen-dependent degradation domain of hypoxia-inducible factor- with oxygen to form hydroxylated C-terminal oxygen-dependent degradation domain and succinate is much slower (approximately 100-fold) than for other similarly studied 2-oxoglutarate oxygenases. Stopped flow/UV-visible spectroscopy experiments demonstrate that the reaction produces a relatively stable species absorbing at 320 nm; Mossbauer spectroscopic experiments indicate that this species is likely not a Fe(IV)=O intermediate, as observed for other 2-oxoglutarate oxygenases. Overall, the results obtained suggest that, at least compared to other studied 2-oxoglutarate oxygenases, prolyl hydroxylase domain 2 reacts relatively slowly with oxygen, a property that may be associated with its function as an oxygen sensor. [copyright sign] 2010 The Authors Journal compilation [copyright sign] 2010 FEBS.
机译：动物对缺氧的反应是由缺氧诱导的转录因子介导的。人缺氧诱导因子受四种Fe（II）和2-氧戊二酸酯依赖性加氧酶的调节：脯氨酰羟化酶结构域酶1-3催化缺氧诱导因子中两个脯氨酰残基的羟化作用，触发其被蛋白酶体降解。抑制缺氧诱导因子的因子催化缺氧诱导因子中天冬酰胺残基的羟基化，从而抑制其转录活性。集体地，低氧诱导因子羟化酶响应于增加的氧浓度而负调节低氧诱导因子。脯氨酰羟化酶结构域2是人类细胞中最重要的氧传感器;但是，脯氨酰羟化酶域2的氧感应功能的潜在动力学基础尚不清楚。我们报告了脯氨酰羟化酶域2与氧气反应的分析。化学猝灭/ MS实验表明脯氨酰羟化酶结构域2，Fe（II），2-氧戊二酸和缺氧诱导因子的C端氧依赖性降解域的复合物与氧反应形成羟基化的C端氧依赖的降解域和琥珀酸比其他类似研究的2-氧戊二酸加氧酶要慢得多（约100倍）。停止流/紫外可见光谱实验表明，该反应产生了一个相对稳定的物种，在320 nm处吸收; Mossbauer光谱实验表明，该物种可能不是Fe（IV）= O中间体，正如其他2-氧代戊二酸加氧酶所观察到的那样。总的来说，获得的结果表明，至少与其他研究的2-氧代戊二酸加氧酶相比，脯氨酰羟化酶结构域2与氧的反应相对缓慢，该性质可能与其作为氧传感器的功能有关。 [版权符号] 2010作者期刊汇编[版权符号] 2010 FEBS。

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