Choreographing an enzyme's dance.
Choreographing an enzyme's dance.
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编排酶的舞蹈。
DOI：
10.1016/j.cbpa.2010.08.007
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发表时间：
2010
影响因子：
7.8
通讯作者：
Kern,Dorothee
中科院分区：
文献类型：
--
作者：
Villali,Janice;Kern,Dorothee
虽然基态结构结合化学工具和酶动力学提供了有用的信息，可能的化学机制的酶催化，他们没有解开精细平衡的能量库存来解释令人印象深刻的速率增强酶。为了实现这一目标，需要以能量景观的形式完整描述酶催化。由于催化的速率是由一系列能量势垒的攀登决定的，我们在这里集中讨论过渡途径的关键问题。时间分辨NMR和模拟的结合使人们得以一瞥蛋白质如何在天然构象的集合中如此有效地移动，同时避免在该旅程中展开。由于原生接触的断裂而导致的能量损失在转变期间由非原生瞬时氢键补偿，从而“保持”能量，直到形成限定替代功能状态的新原生接触。使用动力学同位素效应（KIE）来研究化学步骤表明，由于蛋白质组分对距离的极端敏感性，蛋白质组分的协调原子波动决定了“正确”距离和方向的概率。这里的例子强调了一点，高度编排的构象采样与化学完整性是有效的酶催化的先决条件。
While ground state structures combined with chemical tools and enzyme kinetics deliver useful information on possible chemical mechanisms of enzyme catalysis, they do not unravel the finely balanced energy inventory to explain the impressive rate enhancement of enzymes. For this goal, a complete description of enzyme catalysis in the form of an energy landscape is needed. Since the rate of catalysis is determined by the climb over a sequence of energy barriers, we focus here on the critical question of transition pathways. A combination of time-resolved NMR and simulation deliver a glimpse into how proteins can so efficiently move within the ensemble of the native conformations while avoiding unfolding during that journey. The loss of energy due to breakage of native contacts is compensated by non-native transient hydrogen bonds during the transition thereby ‘holding on’ to the energy until the new native contacts form that define the alternate functional state. The use of kinetic isotope effects (KIE) to study the chemical step show that coordinated atomic fluctuations of the protein component dictate the probability of ‘correct’ distance and orientation, due to its extreme sensitivity to distance. The examples here stress the point that highly choreographed conformational sampling together with chemical integrity is a prerequisite for efficient enzyme catalysis.