在低氧诱导因素中解码的控制
Jingjing Zhuang1, Qinghong Shang2, Fraydoon Rastinejad3
1Marine College, Shandong University, Weihai 264209, China; Helmholtz International Lab, State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China.
Journal of molecular biology
|November 7, 2023
概括
基本的螺旋环-螺旋-PER-ARNT-SIM (bHLH-PAS) 蛋白调节细胞反应. 了解它们的结构和全性机制,特别是缺氧诱导因子 (HIF),有望发现新的治疗药物.
科学领域:
- 分子生物学分子生物学
- 结构生物学是结构生物学.
- 生物化学 生化学
背景情况:
- 哺乳动物bHLH-PAS转录因子感知环境和生理信号.
- 这些蛋白质通过bHLH域形成二元,用于DNA结合.
- bHLH-PAS家族与主要的人类疾病有关,具有治疗点.
研究的目的:
- 审查bHLH-PAS蛋白的HIF亚家族的结构和性机制.
- 突出针对性小分子药物开发的潜力.
主要方法:
- 分析HIF-α蛋白质的晶体结构及其与ARNT的相互作用.
- 通过小分子对质调节的最新发现的审查.
主要成果:
- HIF-α蛋白质的晶体结构揭示了它们与ARNT的相互作用.
- 与PAS-B域结合的小分子在异质上调节HIF-α转录活性.
- 像Belzutifan和Tapinarof这样的批准药物针对bHLH-PAS蛋白质.
结论:
- 了解bHLH-PAS蛋白质架构和全ostery是药物发现的关键.
- 针对PAS领域的带结合腔,使得新疗法的开发成为可能.
- 这一领域的进展为治疗与bHLH-PAS功能障碍相关的疾病提供了有希望的途径.
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