Electric fields imbue enzyme reactivity by aligning active site fragment orbitals

• 成果类型: Article
• 署名作者: Eberhart, M. E.; Wilson, Timothy R.; Jones, T. E.; Alexandrova, Anastassia N.
• 署名单位: Colorado School of Mines; United States Department of Energy (DOE); Los Alamos National Laboratory; University of California System; University of California Los Angeles
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9721
• DOI: 10.1073/pnas.2411976121
• 发表日期: 2024-10-25
• 关键词: electrostatic catalysis; heme; oxidation

摘要

It is broadly recognized that intramolecular electric fields, produced by the protein scaffold and acting on the active site, facilitate enzymatic catalysis. This field effect can be described by several theoretical models, each of which is intuitive to varying degrees. In this contribution, we show that a fundamental effect of electric fields is to generate electrostatic potentials that facilitate the energetic alignment of reactant frontier orbitals. We apply this model to demystify the impact of electric fields on high-valent Specifically, we show that this model easily accounts for the observed field-induced changes to the spin distribution within peroxidase active sites and explains the transition models. Thus, for the intuitive interpretation of the chemical effect of the field, the strategy involves analyzing the response of the orbitals of active site fragments, and their energetic alignment. We note that the energy difference between fragment orbitals involved in charge redistribution acts as a measure for the chemical hardness/softness of the reactive complex. This measure, and its sensitivity to electric fields, offers a single parameter model from which to quantitatively assess the effects of electric fields on reactivity and selectivity. Thus, the model provides an additional perspective to describe electrostatic preorganization and offers ways for its manipulation.