Pineda J R E T, Schwartz S D
Department of Biophysics, Seaver Foundation Center for Bioinformatics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Philos Trans R Soc Lond B Biol Sci. 2006 Aug 29;361(1472):1433-8. doi: 10.1098/rstb.2006.1877.
This manuscript describes ongoing research on the nature of chemical reactions in enzymes. We will investigate how protein dynamics can couple to chemical reaction in an enzyme. We first investigate in some detail why transition state theory cannot fully describe the dynamics of chemical reactions catalysed by enzymes. We describe quantum theories of chemical reaction in condensed phase including studies of how the symmetry of coupled vibrational modes differentially affects reaction dynamics. We make reference to previous work in our group on a variety of condensed phase chemical reactions (liquid and crystalline) and a variety of enzymatically catalysed reactions including the reactions of lactate dehydrogenase and purine nucleoside phosphorylase. All the protein motions we have studied have been quite rapid. We will propose methods to find motions over a broad range of time-scales in enzymes that couple to chemical catalysis. We report recent findings which show that conformational fluctuations in lactate dehydrogenase can strongly affect its ability to catalyse reactions through protein motion, and that only a tiny minority of conformations appear to be catalytically competent.
本手稿描述了关于酶中化学反应本质的正在进行的研究。我们将研究蛋白质动力学如何与酶中的化学反应相耦合。我们首先详细研究为什么过渡态理论不能完全描述酶催化的化学反应的动力学。我们描述了凝聚相化学反应的量子理论，包括对耦合振动模式的对称性如何不同地影响反应动力学的研究。我们参考了我们小组之前关于各种凝聚相化学反应（液体和晶体）以及各种酶催化反应的工作，包括乳酸脱氢酶和嘌呤核苷磷酸化酶的反应。我们研究过的所有蛋白质运动都相当迅速。我们将提出方法来寻找酶中与化学催化相耦合的广泛时间尺度上的运动。我们报告了最近的发现，这些发现表明乳酸脱氢酶中的构象波动可以通过蛋白质运动强烈影响其催化反应的能力，并且只有极少数构象似乎具有催化活性。
