Chaturvedi Shobhit S, Bím Daniel, Christov Christo Z, Alexandrova Anastassia N
Department of Chemistry and Biochemistry, University of California, Los Angeles California 90095 USA
Department of Chemistry, Michigan Technological University Houghton Michigan 49931 USA.
Chem Sci. 2023 Sep 13;14(40):10997-11011. doi: 10.1039/d3sc02982d. eCollection 2023 Oct 18.
Enzymes are versatile and efficient biological catalysts that drive numerous cellular processes, motivating the development of enzyme design approaches to tailor catalysts for diverse applications. In this perspective, we investigate the unique properties of natural, evolved, and designed enzymes, recognizing their strengths and shortcomings. We highlight the challenges and limitations of current enzyme design protocols, with a particular focus on their limited consideration of long-range electrostatic and dynamic effects. We then delve deeper into the impact of the protein environment on enzyme catalysis and explore the roles of preorganized electric fields, second coordination sphere interactions, and protein dynamics for enzyme function. Furthermore, we present several case studies illustrating successful enzyme-design efforts incorporating enzyme strategies mentioned above to achieve improved catalytic properties. Finally, we envision the future of enzyme design research, spotlighting the challenges yet to be overcome and the synergy of intrinsic electric fields, second coordination sphere interactions, and conformational dynamics to push the state-of-the-art boundaries.
酶是多功能且高效的生物催化剂，驱动着众多细胞过程，这促使人们开发酶设计方法，以便为各种应用量身定制催化剂。从这个角度出发，我们研究天然、进化和设计酶的独特性质，认识到它们的优点和缺点。我们强调了当前酶设计方案的挑战和局限性，特别关注其对长程静电和动态效应的有限考虑。然后，我们更深入地探讨蛋白质环境对酶催化的影响，并探索预组织电场、第二配位层相互作用和蛋白质动力学在酶功能中的作用。此外，我们还介绍了几个案例研究，展示了成功的酶设计工作，这些工作结合了上述酶策略以实现改进的催化性能。最后，我们展望了酶设计研究的未来，突出了有待克服的挑战以及内在电场、第二配位层相互作用和构象动力学之间的协同作用，以推动现有技术的边界。
