在素样和逆转录病毒的阿斯巴拉特蛋白酶中,进化保存了功能机制
Michele Cascella1, Cristian Micheletti, Ursula Rothlisberger
1International School for Advanced Studies, INFM-DEMOCRITOS Modeling Center for Research in Atomistic Simulation, Via Beirut 2-4, 34014 Trieste, Italy.
Journal of the American Chemical Society
|March 18, 2005
概括
像HIV-1蛋白酶一样,阿斯巴拉特蛋白酶利用形状灵活性来发挥功能. 保存的残留物通过大规模的运动来调节酶活性,这是aspartic蛋白酶家族中常见的机制.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 酶学 是一种酶学.
背景情况:
- 艾滋病毒-1酸蛋白酶的功能与其结构灵活性有关.
- 像素的酸蛋白酶具有保存的结构特征.
研究的目的:
- 为了研究形状灵活性是否影响素类酸蛋白酶的功能.
- 为了确定保存的残留物及其在酶活性中的作用.
主要方法:
- 序列对齐以识别保存的残留物.
- 经典分子动力学 (MD) 模拟.
- 免费能源计算.
- 基于拓的能源功能分析.
主要成果:
- 保存的残留物聚集在三个关键区域:活动地点附近,β片和暴露于溶剂的区域.
- 保存区域,尽管移动性较低,驱动大规模的蛋白质运动,影响基质-催化酸距离.
- 酶激活的自由能量受到这些大规模运动的显著影响.
- 在真核细胞和逆转录病毒中存在一种常见的酶活性调节机制.
结论:
- 酸蛋白酶采用一种保留的结构灵活性机制来调节酶活性.
- 进化选择了类似的功能运动在阿斯巴拉特蛋白质酶,尽管在他们的折叠变化.
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