Hammes-Schiffer Sharon, Benkovic Stephen J
Department of Chemistry, Pennsylvania State University, University Park, Pennsylvania 16802, USA.
Annu Rev Biochem. 2006;75:519-41. doi: 10.1146/annurev.biochem.75.103004.142800.
This review examines the linkage between protein conformational motions and enzyme catalysis. The fundamental issues related to this linkage are probed in the context of two enzymes that catalyze hydride transfer, namely dihydrofolate reductase and liver alcohol dehydrogenase. The extensive experimental and theoretical studies addressing the role of protein conformational changes in these enzyme reactions are summarized. Evidence is presented for a network of coupled motions throughout the protein fold that facilitate the chemical reaction. This network is comprised of fast thermal motions that are in equilibrium as the reaction progresses along the reaction coordinate and that lead to slower equilibrium conformational changes conducive to the chemical reaction.
本综述探讨了蛋白质构象运动与酶催化之间的联系。在两种催化氢化物转移的酶，即二氢叶酸还原酶和肝脏乙醇脱氢酶的背景下，探究了与这种联系相关的基本问题。总结了针对蛋白质构象变化在这些酶反应中的作用所进行的广泛实验和理论研究。有证据表明，在整个蛋白质折叠结构中存在一个耦合运动网络，该网络促进化学反应。这个网络由快速的热运动组成，随着反应沿着反应坐标进行，这些热运动处于平衡状态，并导致有利于化学反应的较慢的平衡构象变化。
