Computational Biology Institute, and Computer Science and Mathematics Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, USA.
Microb Cell Fact. 2006 Jan 12;5:2. doi: 10.1186/1475-2859-5-2.
Microbes utilize enzymes to perform a variety of functions. Enzymes are biocatalysts working as highly efficient machines at the molecular level. In the past, enzymes have been viewed as static entities and their function has been explained on the basis of direct structural interactions between the enzyme and the substrate. A variety of experimental and computational techniques, however, continue to reveal that proteins are dynamically active machines, with various parts exhibiting internal motions at a wide range of time-scales. Increasing evidence also indicates that these internal protein motions play a role in promoting protein function such as enzyme catalysis. Moreover, the thermodynamical fluctuations of the solvent, surrounding the protein, have an impact on internal protein motions and, therefore, on enzyme function. In this review, we describe recent biochemical and theoretical investigations of internal protein dynamics linked to enzyme catalysis. In the enzyme cyclophilin A, investigations have lead to the discovery of a network of protein vibrations promoting catalysis. Cyclophilin A catalyzes peptidyl-prolyl cis/trans isomerization in a variety of peptide and protein substrates. Recent studies of cyclophilin A are discussed in detail and other enzymes (dihydrofolate reductase and liver alcohol dehydrogenase) where similar discoveries have been reported are also briefly discussed. The detailed characterization of the discovered networks indicates that protein dynamics plays a role in rate-enhancement achieved by enzymes. An integrated view of enzyme structure, dynamics and function have wide implications in understanding allosteric and co-operative effects, as well as protein engineering of more efficient enzymes and novel drug design.
微生物利用酶来执行各种功能。酶是在分子水平上作为高效机器工作的生物催化剂。过去，酶被视为静态实体，其功能是基于酶与底物之间的直接结构相互作用来解释的。然而，各种实验和计算技术不断揭示出蛋白质是动态活跃的机器，其各个部分在广泛的时间尺度上表现出内部运动。越来越多的证据还表明，这些内部蛋白质运动在促进酶催化等蛋白质功能中发挥作用。此外，溶剂对蛋白质的热力学波动会影响内部蛋白质运动，从而影响酶的功能。在这篇综述中，我们描述了与酶催化相关的内部蛋白质动力学的最新生化和理论研究。在亲环素 A 酶中，研究导致了促进催化的蛋白质振动网络的发现。亲环素 A 催化各种肽和蛋白质底物中的肽基脯氨酰顺/反异构化。详细讨论了亲环素 A 的最新研究，并简要讨论了其他报道了类似发现的酶（二氢叶酸还原酶和肝醇脱氢酶）。所发现的网络的详细特征表明，蛋白质动力学在酶实现速率增强中发挥作用。对酶的结构、动力学和功能的综合了解具有广泛的意义，可用于理解变构和协同效应，以及更高效酶的蛋白质工程和新型药物设计。
