An Enzyme Model Which Mimics Chymotrypsin and N‑Terminal Hydrolases

Enzymes are the most efficient and specific catalysts to date. Although they have been thoroughly studied for years, building a true enzyme mimic remains a challenging and necessary task. Here, we show how a three-dimensional geometry analysis of the key catalytic residues in natural hydrolases has...

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Bibliographic Details
Published in:ACS catalysis Vol. 10; no. 19; pp. 11162 - 11170
Main Authors: Garrido-González, José J, Iglesias Aparicio, M, García, Miguel Martínez, Simón, Luis, Sanz, Francisca, Morán, Joaquín R, Fuentes de Arriba, Ángel L
Format: Journal Article
Language:English
Published: American Chemical Society 02-10-2020
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Summary:Enzymes are the most efficient and specific catalysts to date. Although they have been thoroughly studied for years, building a true enzyme mimic remains a challenging and necessary task. Here, we show how a three-dimensional geometry analysis of the key catalytic residues in natural hydrolases has been exploited to design and synthesize small-molecule artificial enzymes which mimic the active centers of chymotrypsin and N-terminal hydrolases. The optimized prototype catalyzes the methanolysis of the acyl enzyme mimic with a half-life of only 3.7 min at 20 °C, and it is also able to perform the transesterification of vinyl acetate at room temperature. DFT studies and X-ray diffraction analysis of the catalyst bound to a transition state analogue proves the similarity with the geometry of natural hydrolases.
ISSN:2155-5435
2155-5435
DOI:10.1021/acscatal.0c02121