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Simulating the Catalytic Effect of a Designed Mononuclear Zinc Metalloenzyme that Catalyzes the Hydrolysis of Phosphate Triesters
[Image: see text] One of the greatest challenges in biotechnology and in biochemistry is the ability to design efficient enzymes. In fact, such an ability would be one of the most convincing manifestations of a full understanding of the origin of enzyme catalysis. Despite some progress on this front...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical
Society
2014
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207531/ https://www.ncbi.nlm.nih.gov/pubmed/25233046 http://dx.doi.org/10.1021/jp507592g |
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author | Singh, Manoj Kumar Chu, Zhen T. Warshel, Arieh |
author_facet | Singh, Manoj Kumar Chu, Zhen T. Warshel, Arieh |
author_sort | Singh, Manoj Kumar |
collection | PubMed |
description | [Image: see text] One of the greatest challenges in biotechnology and in biochemistry is the ability to design efficient enzymes. In fact, such an ability would be one of the most convincing manifestations of a full understanding of the origin of enzyme catalysis. Despite some progress on this front, most of the advances have been made by placing the reacting fragments in the proper places rather than by optimizing the preorganization of the environment, which is the key factor in enzyme catalysis. A rational improvement of the preorganization and a consistent assessment of the effectiveness of different design options require approaches capable of evaluating reliably the actual catalytic effect. In this work we examine the ability of the empirical valence bond (EVB) to reproduce the results of directed evolution improvements of the catalysis of diethyl 7-hydroxycoumarinyl by a designed mononuclear zinc metalloenzyme. Encouragingly, our study reproduced the catalytic effect obtained by directed evolution and offers a good start for further studies of this system. |
format | Online Article Text |
id | pubmed-4207531 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | American Chemical
Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-42075312015-09-18 Simulating the Catalytic Effect of a Designed Mononuclear Zinc Metalloenzyme that Catalyzes the Hydrolysis of Phosphate Triesters Singh, Manoj Kumar Chu, Zhen T. Warshel, Arieh J Phys Chem B [Image: see text] One of the greatest challenges in biotechnology and in biochemistry is the ability to design efficient enzymes. In fact, such an ability would be one of the most convincing manifestations of a full understanding of the origin of enzyme catalysis. Despite some progress on this front, most of the advances have been made by placing the reacting fragments in the proper places rather than by optimizing the preorganization of the environment, which is the key factor in enzyme catalysis. A rational improvement of the preorganization and a consistent assessment of the effectiveness of different design options require approaches capable of evaluating reliably the actual catalytic effect. In this work we examine the ability of the empirical valence bond (EVB) to reproduce the results of directed evolution improvements of the catalysis of diethyl 7-hydroxycoumarinyl by a designed mononuclear zinc metalloenzyme. Encouragingly, our study reproduced the catalytic effect obtained by directed evolution and offers a good start for further studies of this system. American Chemical Society 2014-09-18 2014-10-23 /pmc/articles/PMC4207531/ /pubmed/25233046 http://dx.doi.org/10.1021/jp507592g Text en Copyright © 2014 American Chemical Society Terms of Use (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) |
spellingShingle | Singh, Manoj Kumar Chu, Zhen T. Warshel, Arieh Simulating the Catalytic Effect of a Designed Mononuclear Zinc Metalloenzyme that Catalyzes the Hydrolysis of Phosphate Triesters |
title | Simulating the Catalytic Effect of a Designed Mononuclear
Zinc Metalloenzyme that Catalyzes the Hydrolysis of Phosphate Triesters |
title_full | Simulating the Catalytic Effect of a Designed Mononuclear
Zinc Metalloenzyme that Catalyzes the Hydrolysis of Phosphate Triesters |
title_fullStr | Simulating the Catalytic Effect of a Designed Mononuclear
Zinc Metalloenzyme that Catalyzes the Hydrolysis of Phosphate Triesters |
title_full_unstemmed | Simulating the Catalytic Effect of a Designed Mononuclear
Zinc Metalloenzyme that Catalyzes the Hydrolysis of Phosphate Triesters |
title_short | Simulating the Catalytic Effect of a Designed Mononuclear
Zinc Metalloenzyme that Catalyzes the Hydrolysis of Phosphate Triesters |
title_sort | simulating the catalytic effect of a designed mononuclear
zinc metalloenzyme that catalyzes the hydrolysis of phosphate triesters |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207531/ https://www.ncbi.nlm.nih.gov/pubmed/25233046 http://dx.doi.org/10.1021/jp507592g |
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