Incorporating Fast Protein Dynamics into Enzyme Design: A Proposed Mutant Aromatic Amine Dehydrogenase

In recent years, there has been encouraging progress in the engineering of enzymes that are designed to catalyze reactions not accelerated by natural enzymes. We tested the possibility of reengineering an existing enzyme by introducing a fast protein motion that couples to the reaction. Aromatic ami...

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Bibliographic Details
Published in:The journal of physical chemistry. B 2017-08, Vol.121 (30), p.7290-7298
Main Authors: Zoi, Ioanna, Antoniou, Dimitri, Schwartz, Steven D
Format: Article
Language:English
Subjects:
Biocatalysis
Catalytic Domain
Models, Molecular
Oxidoreductases Acting on CH-NH Group Donors - chemistry
Oxidoreductases Acting on CH-NH Group Donors - genetics
Oxidoreductases Acting on CH-NH Group Donors - metabolism
Protein Engineering
Quantum Theory
Substrate Specificity
Tryptamines - chemistry
Tryptamines - metabolism
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Summary:In recent years, there has been encouraging progress in the engineering of enzymes that are designed to catalyze reactions not accelerated by natural enzymes. We tested the possibility of reengineering an existing enzyme by introducing a fast protein motion that couples to the reaction. Aromatic amine dehydrogenase is a system that has been shown to use a fast substrate motion as part of the reaction mechanism. We identified a mutation that preserves this fast motion but also introduces a favorable fast motion near the active site that did not exist in the native enzyme. Transition path sampling was used for the analysis of the atomic details of the mechanism.
ISSN:1520-6106
1520-5207
DOI:10.1021/acs.jpcb.7b05319