PROTON TUNNELING IN ENZYME REACTIONS

生物氢转移中的量子效应将被表征 利用新开发的多重同位素标记技术， 半经典Swain-经典Swain-Schaad关系的崩溃。 磷酸丙糖异构酶（TIM）催化的质子转移反应， 经过充分表征并提供了一个独特的系统来检查质子 酶反应中的隧道效应和耦合质子运动。 小学和 对于TIM，将测量次级氢动力学同位素效应 反应和相应的非酶催化反应。 效果 改变势垒宽度和活性中心酸=碱的方向 催化剂对质子隧穿将使用以下技术进行检查： 定点诱变。 BEBOVIB-IV程序将用于执行 模型反应物、产物和过渡态的正态分析 反应协调频率和同位素效应的结构 将被模仿。 关于酶的当前想法和模型的测试 催化包括回答反应如何与质子配位的问题 运动耦合到非转移质子的运动，并耦合到非转移质子的运动。 蛋白质的振动运动，反应坐标频率如何变化， 对于酶和非酶催化反应，以及酶是否降低 质子转移到碳和从碳转移的固有障碍。

Quantum effects in biological hydrogen transfers will be characterized using a newly-developed technique of multiple isotopic labeling to measure a breakdown in the semi-classical Swain-classical Swain-Schaad relation. The proton transfers catalyzed by triosephosphate isomerase (TIM) have been well characterized and provide a unique system with which to examine proton tunneling and coupled proton motion in enzyme reactions. Primary and secondary hydrogen kinetic isotope effects will be measured for the TIM reaction and the corresponding non-enzyme-catalyzed reactions. The effect of changing the barrier width and orientation of the active-site acid=base catalysts on proton tunneling will be examined using the techniques of site-directed mutagenesis. The program BEBOVIB-IV will be used to perform a normal mode analysis of model reactants, products, and transition-state structures from which reaction-coordinate frequencies and isotope effects will be modeled. Tests of current ideas and models regarding enzyme catalysis include answering questions as to how reaction-coordinate proton motions are coupled to the motion of non-transferred protons and to the vibrational motions of proteins, how reaction-coordinate frequencies vary for enzyme and non-enzyme-catalyzed reactions, and whether enzymes lower the intrinsic barriers for proton transfer to and from carbon.