在HIV-1蛋白酶的灵活的富含Gly的片内,快速的类 cis-trans 异构
Donald Hamelberg1, J Andrew McCammon
1Howard Hughes Medical Institute, Center for Theoretical Biological Physics, Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093, USA. dhamelbe@mccammon.ucsd.edu
Journal of the American Chemical Society
|October 6, 2005
概括
这是HIV-1蛋白酶.
科学领域:
- 分子生物学分子生物学
- 生物物理学的生物物理.
- 结构生物学是结构生物学.
背景情况:
- 人类免疫缺陷病毒1型 (HIV-1) 蛋白酶对于病毒复制至关重要.
- 它的活性部位由柔性板调节,但这种柔性的原子化机制尚不清楚.
- 了解膜动态对于开发有效的抗病毒疗法至关重要.
研究的目的:
- 阐明HIV-1蛋白酶的灵活性背后的原子化机制.
- 研究富含甘氨酸的区域和特定键在动态中的作用.
- 探索二次结构对分子过程动力学的影响.
主要方法:
- 计算模拟用于分析分子动力学.
- 研究Gly-Gly欧米茄键的 cis-trans 异体化.
- 研究环形成及其对异构化速率的影响.
主要成果:
- 富含甘氨酸的HIV-1蛋白酶片尖端中的Gly-Gly欧米茄键表现出异常快速的cis-trans异构.
- 这种快速的异构化发生在微秒到毫秒的时间尺度上,比典型的速度快得多.
- 标尖的β-hairpin循环结构被确定为这种加速异构化的原因.
结论:
- 艾滋病毒-1蛋白酶的灵活性是由快速的Gly-Gly键同质化驱动的.
- 在片尖上的β-hairpin循环形成意外地加快了这种异体化过程.
- 这些发现为病毒蛋白酶和潜在药物点的动态机制提供了新的见解.
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