Agarwal Pratul K, Bernard David N, Bafna Khushboo, Doucet Nicolas
Department of Physiological Sciences and High-Performance Computing Center, Oklahoma State University, Stillwater, Oklahoma 74078.
Arium BioLabs, 2519 Caspian Drive, Knoxville, Tennessee 37932.
ChemCatChem. 2020 Oct 6;12(19):4704-4720. doi: 10.1002/cctc.202000665. Epub 2020 Jun 26.
Conventional understanding of how enzymes function strongly emphasizes the role of structure. However, increasing evidence clearly indicates that enzymes do not remain fixed or operate exclusively in or close to their structure. Different parts of the enzyme (from individual residues to full domains) undergo concerted motions on a wide range of time-scales, including that of the catalyzed reaction. Information obtained on these internal motions and conformational fluctuations has so far uncovered and explained many aspects of enzyme mechanisms, which could not have been understood from a single structure alone. Although there is wide interest in understanding enzyme dynamics and its role in catalysis, several challenges remain. In addition to technical difficulties, the vast majority of investigations are performed in dilute aqueous solutions, where conditions are significantly different than the cellular milieu where a large number of enzymes operate. In this review, we discuss recent developments, several challenges as well as opportunities related to this topic. The benefits of considering dynamics as an integral part of the enzyme function can also enable new means of biocatalysis, engineering enzymes for industrial and medicinal applications.
传统上对酶如何发挥功能的理解非常强调结构的作用。然而，越来越多的证据清楚地表明，酶并非保持固定不变，也并非仅在其结构内部或附近起作用。酶的不同部分（从单个残基到整个结构域）在广泛的时间尺度上进行协同运动，包括催化反应的时间尺度。到目前为止，从这些内部运动和构象波动中获得的信息揭示并解释了酶作用机制的许多方面，而仅从单一结构是无法理解这些方面的。尽管人们对理解酶动力学及其在催化中的作用有着广泛的兴趣，但仍存在一些挑战。除了技术难题外，绝大多数研究是在稀水溶液中进行的，那里的条件与大量酶发挥作用的细胞环境有很大不同。在这篇综述中，我们讨论了与该主题相关的最新进展、一些挑战以及机遇。将动力学视为酶功能不可或缺的一部分所带来的好处还可以催生新的生物催化手段，为工业和医学应用设计工程酶。
