Enhanced active-site electric field accelerates enzyme catalysis.

ABSTRACT: The design and improvement of enzymes based on physical principles remain challenging. Here we demonstrate that the principle of electrostatic catalysis can be leveraged to substantially improve a natural enzyme's activity. We enhanced the active-site electric field in horse liver alcohol dehydrogenase by replacing the serine hydrogen-bond donor with threonine and replacing the catalytic Zn²⁺ with Co²⁺. Based on the electric field enhancement, we make a quantitative prediction of rate acceleration-50-fold faster than the wild-type enzyme-which was in close agreement with experimental measurements. The effects of the hydrogen bonding and metal coordination, two distinct chemical forces, are described by a unified physical quantity-electric field, which is quantitative,

SUBMITTER: Zheng C 

PROVIDER: S-EPMC10906027 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature