(+) -α-平烯与人类细胞染色体P450 2B6结合的结构和热力学基础
P Ross Wilderman1, Manish B Shah, Hyun-Hee Jang
1Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California 92093, United States. pwilderman@ucsd.edu
Journal of the American Chemical Society
|June 22, 2013
概括
人类P450 2B6结合 (+) -α-pinene,由于酶的灵活性和度,它具有很高的亲和力. 这项研究揭示了碳化合物与细胞P450酶相互作用的关键结构和热力学见解.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 细胞染色体P450酶对于药物代谢至关重要.
- (+) -α-Pinene是P450 2B酶的一个强有力的抑制剂.
- 了解碳化合物与P450s的结合仍然是一个挑战.
研究的目的:
- 阐明人类P450 2B6和 (+) -α-pinene之间高亲和度结合的分子基础.
- 研究这种相互作用的热力学和结构决定因素.
主要方法:
- 综合生物物理和结构分析.
- I型光谱转移试验以确认结合.
- 异热定位热量计 (ITC) 用于热力学分析.
- 在2.0 Å分辨率的P450 2B6-(+) -α-pinene复合物的X射线晶体学.
主要成果:
- (+) -α-Pinene与P450 2B6结合,通过I型光谱偏移表示.
- 与P450 2B6的结合是由和驱动的,与P450 2A6不同,在其中占主导地位.
- 晶体结构揭示了灵活的P450 2B6活性部位在带结合时显著的蛋白质重组.
结论:
- 在P450 2B6中的酶灵活性在对高亲和度碳化合物结合的体贡献中起着至关重要的作用.
- 这项研究提供了对抑制剂与细胞染色体P450结合的结构基础的原子层次见解.
- 这些发现有助于更好地理解控制P450与碳化合物的相互作用的化学和结构决定因素.
相关概念视频
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Cycloheptatriene is a neutral monocyclic unsaturated hydrocarbon that consists of an odd number of carbon atoms and an intervening sp3 carbon in the ring. The three double bonds in the ring correspond to 6 π electrons, which is a Huckel number, and therefore satisfies the criteria of 4n + 2 π electrons. However, the intervening sp3 carbon disrupts the continuous overlap of p orbitals. As a result, cycloheptatriene is not aromatic.
Removing one hydrogen from the intervening CH2 group with both...
Removing one hydrogen from the intervening CH2 group with both...
01:18Aromatic Hydrocarbon Anions: Structural Overview
Neutral hydrocarbons like cyclopentadiene with an odd number of carbon atoms and one intervening CH2 group in the ring are not aromatic. Cyclopentadiene with 4 π electrons does not satisfy the 4n + 2 π electron rule. Additionally, the intervening CH2 group is sp3 hybridized and lacks a vacant p orbital, thereby interrupting the overlap of p orbitals in a continuous manner and preventing the delocalization of π electrons throughout the ring.
Due to the absence of continuous overlap of p...
Due to the absence of continuous overlap of p...
01:24π Molecular Orbitals of 1,3-Butadiene
Conjugated dienes have lower heats of hydrogenation than cumulated and isolated dienes, making them more stable. The enhanced stabilization of conjugated systems can be understood from their π molecular orbitals.
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01:29UV–Vis Spectroscopy: Woodward–Fieser Rules
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