指核的活性:分析蛋白质包装和静电选
1Frederick Cancer Research and Development Center, Screening Technologies Branch, DCTD, NCI, NIH, SAIC, Frederick, Maryland 21702, USA. covell@faxpdc.ncifcrf.gov
Journal of the American Chemical Society
|July 18, 2001
概括
指进化为屏蔽反应性硫酸盐,其稳定性因蛋白质环境而异. 不稳定的指,就像在人类雌激素受体中一样,可能会被氧化还原调节,影响转录和癌症进展.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 生物有机化学 生物有机化学
背景情况:
- 指是参与DNA结合和蛋白质与蛋白质相互作用的关键蛋白质图案.
- 它们的化学稳定性受到周围蛋白质环境的影响.
- 了解指的反应性是解读它们多样化的生物功能的关键.
研究的目的:
- 根据蛋白质包装和芯的静电选,评估指的化学稳定性.
- 预测相对指的反应性和评估功能差异.
- 研究指稳定性在生物调节和疾病中的作用.
主要方法:
- 从92个实验性蛋白质结构中分析了207个指.
- 评估蛋白质包装和芯的静电选.
- 确定稳定相互作用,包括键和盐桥.
- 基于核心选的指反应性的预测.
主要成果:
- 指通常可以屏蔽潜在的反应性核心硫酸盐,并增加对阳离子核心图案的选.
- 酶性芯通过负静电选来区分.
- 骨干:核心NH-S键和保存的残留物稳定了指核心.
- 不稳定的指表现出不良选的核心,表明氧化还原或金属氨酸 (MT) 调节.
- 核受体的C端指,特别是人类雌激素受体 (hER),预计将是高度可变的.
结论:
- 指进化促进反应性硫酸盐的屏蔽,通过静电选进行功能差异化.
- 指的检测不良可能表明氧化还原或MT调节的功能.
- 人类雌激素受体的C端指被预测是不稳定和氧化还原调节的,可能会影响转录和乳腺癌的进展.
- 弱电友性剂可能会抑制hER介导的转录.
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