Schramm Vern L
Department of Biochemistry, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, NY 10461, United States.
Curr Opin Chem Biol. 2007 Oct;11(5):529-36. doi: 10.1016/j.cbpa.2007.07.013. Epub 2007 Sep 14.
Kinetic isotope effects are increasingly applied to investigate enzyme reactions and have been used to understand transition state structure, reaction mechanisms, quantum mechanical hydride ion tunneling and to design transition state analogue inhibitors. Binding isotope effects are an inherent part of most isotope effect measurements but are usually assumed to be negligible. More detailed studies have established surprisingly large binding isotope effects with lactate dehydrogenase, hexokinase, thymidine phosphorylase, and purine nucleoside phosphorylase. Binding reactants into catalytic sites immobilizes conformationally flexible groups, polarizes bonds, and distorts bond angle geometry, all of which generate binding isotope effects. Binding isotope effects are easily measured and provide high-resolution and detailed information on the atomic changes resulting from ligand-macromolecular interactions. Although binding isotope effects complicate kinetic isotope effect analysis, they also provide a powerful tool for finding atomic distortion in molecular interactions.
动力学同位素效应越来越多地应用于研究酶反应，并已被用于理解过渡态结构、反应机制、量子力学氢负离子隧穿以及设计过渡态类似物抑制剂。结合同位素效应是大多数同位素效应测量中固有的一部分，但通常被认为可以忽略不计。更详细的研究已经证实，乳酸脱氢酶、己糖激酶、胸苷磷酸化酶和嘌呤核苷磷酸化酶存在惊人的大结合同位素效应。将反应物结合到催化位点会固定构象灵活的基团，使键极化，并扭曲键角几何形状，所有这些都会产生结合同位素效应。结合同位素效应易于测量，并能提供有关配体 - 大分子相互作用导致的原子变化的高分辨率和详细信息。虽然结合同位素效应会使动力学同位素效应分析复杂化，但它们也为发现分子相互作用中的原子畸变提供了一个强大的工具。
