Zoi Ioanna, Antoniou Dimitri, Schwartz Steven D
Department of Biochemistry, University of Arizona , Tucson, Arizona 85721, United States.
J Phys Chem Lett. 2017 Dec 21;8(24):6165-6170. doi: 10.1021/acs.jpclett.7b02989. Epub 2017 Dec 11.
In recent years, there has been much discussion regarding the origin of enzymatic catalysis and whether including protein dynamics is necessary for understanding catalytic enhancement. An important contribution in this debate was made with the application of the vibrational Stark effect spectroscopy to measure electric fields in the active site. This provided a window on electric fields at the transition state in enzymatic reactions. We performed computational studies on two enzymes where we have shown that fast dynamics is part of the reaction mechanism and calculated the electric field near the bond-breaking event. We found that the fast motions that we had identified lead to an increase of the electric field, thus preparing an enzymatic configuration that is electrostatically favorable for the catalytic chemical step. We also studied the enzyme that has been the subject of Stark spectroscopy, ketosteroid isomerase, and found electric fields of a similar magnitude to the two previous examples.
近年来，关于酶催化的起源以及理解催化增强是否需要考虑蛋白质动力学存在诸多讨论。振动斯塔克效应光谱学在测量活性位点电场方面的应用为这场辩论做出了重要贡献。这为酶促反应过渡态的电场提供了一个窗口。我们对两种酶进行了计算研究，结果表明快速动力学是反应机制的一部分，并计算了键断裂事件附近的电场。我们发现，我们所确定的快速运动导致电场增强，从而形成一种对催化化学步骤在静电方面有利的酶构象。我们还研究了斯塔克光谱学的研究对象——酮甾体异构酶，发现其电场强度与前两个例子相似。
