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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Published in: | ACS catalysis Vol. 10; no. 19; pp. 11162 - 11170 |
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Main Authors: | , , , , , , |
Format: | Journal Article |
Language: | English |
Published: |
American Chemical Society
02-10-2020
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Subjects: | |
Online Access: | Get full text |
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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. |
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ISSN: | 2155-5435 2155-5435 |
DOI: | 10.1021/acscatal.0c02121 |