Directed Evolution As a Probe of Rate Promoting Vibrations Introduced Via Mutational Change

Overview

Journal Biochemistry

Specialty Biochemistry

Date 2018 Mar 20

PMID 29553716

Citations 7

Authors

Xi Chen

Steven D Schwartz

Affiliations

Soon will be listed here.

Abstract

In this article, we study with transition path sampling and reaction coordinate analysis how directed evolution in the Kemp eliminase family of artificial enzymes makes differential use of rapid rate promoting vibrations as a component of their chemical mechanism. Even though this family was initially created by placing the expected active site in a fixed protein matrix, we find a shift from largely static to more dynamic active sites that make use of donor-acceptor compression as the evolutionary process proceeds. We see that this introduction of dynamics significantly shifts the order of processes in the reaction. We also suggest that the lack of "design for dynamics" may help explain the relatively low proficiency of such designed enzymes.

Citing Articles

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Engineered Tryptophan Synthase Balances Equilibrium Effects and Fast Dynamic Effects.

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The physical origin of rate promoting vibrations in enzymes revealed by structural rigidity.

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