在涉及碳酸的酶机制中的合成效率:aristolochene synthase
Rudolf K Allemann1, Neil J Young, Shuhua Ma
1School of Chemistry, Cardiff University, Park Place, Cardiff, CF10 3AT, U.K. allemannrk@cf.ac.uk
Journal of the American Chemical Society
|October 9, 2007
概括
通过阿里斯托洛合成酶将法纳西酸 (FPP) 循环转化为 (+) -阿里斯托洛的新机制涉及直接的分子内质子转移,与以前的模型不同. 这种质子转移由酶促进,降低了激活能量,解释了基质的特异性.
科学领域:
- 生物化学和有机化学
- 酵素学和机械学研究
- 计算化学计算化学
背景情况:
- 阿里斯托洛基因合成酶催化了法纳西尔酸盐 (FPP) 的循环转化为 (+) - 亚里斯托洛基因,这是一个关键的基基.
- 之前提出的机制涉及生殖基A作为中间体,但实验证据与此相矛盾.
- 了解精确的催化机制对于阐明烯生物合成途径至关重要.
研究的目的:
- 阐明FPP到 (+) -aristolochene由aristolochene合成酶催化的碳化循环的详细机制.
- 为此酶反应提出的新型分子内质子转移途径的研究.
- 以计算方式建模基质-酶相互作用,并确定参与催化过程中的关键残留物.
主要方法:
- 高层次的初始分子轨道 (MO) 计算.
- 密度函数理论 (DFT) 计算以确定反应路径和能量障碍.
- 基质酶复合物的建模,以分析FPP和aristolochene合成酶之间的相互作用.
主要成果:
- 提出了一种新的分子内质子转移机制,与之前的碳酸传播模型有所不同.
- 直接分子内质子转移的计算障碍约为22 kcal/mol,由酶降低到16-20 kcal/mol.
- 通过酸盐结合的水分子参与的质子穿的替代途径被确定.
- 拟议的机制与实验观察结果一致,即生殖基质A不是基质.
- 计算机建模确定了Trp 334和Phe 178对于基质定位至关重要,这与突变发生的数据一致,这些数据显示突变后产品形状发生了变化.
结论:
- 该研究提出了一种新的分子内质子转移机制,用于阿里斯托洛基因生物合成,得到计算证据的支持.
- 阿里斯托洛合成酶显著降低了这种质子转移的激活屏障,提高了催化效率.
- 特定的氨基酸残留物 (Trp 334, Phe 178) 在基质结合和导向中起着至关重要的作用,指导反应路径并防止异常循环.
相关概念视频
Synthesis of α-Substituted Carbonyl Compounds: The Stork Enamine Reaction
α-Substituted ketones or aldehydes can be synthesized from enamines by the Stork enamine reaction, named after its pioneer Gilbert Stork. Enamines are useful synthetic intermediates where the lone pair on nitrogen is in conjugation with the C=C bond. They resemble enolate ions, as the resonance forms of both species have a nucleophilic α carbon.
Introduction to Mechanisms of Enzyme Catalysis
For many years, scientists thought that enzyme-substrate binding took place in a simple "lock-and-key" fashion. This model stated that the enzyme and substrate fit together perfectly in one instantaneous step. However, current research supports a more refined view scientists call induced fit. The induced-fit model expands upon the lock-and-key model by describing a more dynamic interaction between enzyme and substrate. As the enzyme and substrate come together, their interaction causes a mild...
Introduction to Mechanisms of Enzyme Catalysis
For many years, scientists thought that enzyme-substrate binding took place in a simple "lock-and-key" fashion. This model stated that the enzyme and substrate fit together perfectly in one instantaneous step. However, current research supports a more refined view scientists call induced fit. The induced-fit model expands upon the lock-and-key model by describing a more dynamic interaction between enzyme and substrate. As the enzyme and substrate come together, their interaction causes a mild...
Catalytically Perfect Enzymes
The theory of catalytically perfect enzymes was first proposed by W.J. Albery and J. R. Knowles in 1976. These enzymes catalyze biochemical reactions at high-speed. Their catalytic efficiency values range from 108-109 M-1s-1. These enzymes are also called 'diffusion-controlled' as the only rate-limiting step in the catalysis is that of the substrate diffusion into the active site. Examples include triose phosphate isomerase, fumarase, and superoxide dismutase.
Reduction of Alkenes: Asymmetric Catalytic Hydrogenation
Catalytic hydrogenation of alkenes is a transition-metal catalyzed reduction of the double bond using molecular hydrogen to give alkanes. The mode of hydrogen addition follows syn stereochemistry.
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
Regioselectivity and Stereochemistry of Acid-Catalyzed Hydration
The rate of acid-catalyzed hydration of alkenes depends on the alkene's structure, as the presence of alkyl substituents at the double bond can significantly influence the rate.


