Is Promiscuous CALB a Good Scaffold for Designing New Epoxidases?
Candida Antarctica lipase B (CALB) is a well-known enzyme, especially because of its promiscuous activity. Due to its properties, CALB was widely used as a benchmark for designing new catalysts for important organic reactions. The active site of CALB is very similar to that of soluble epoxide hydrol...
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Online Access: | http://hdl.handle.net/10234/159486 https://doi.org/10.3390/molecules201017789 |
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ftunivjaumeirep:oai:repositori.uji.es:10234/159486 2023-05-15T13:58:37+02:00 Is Promiscuous CALB a Good Scaffold for Designing New Epoxidases? Bordes, Isabel Recatalá, José Świderek, Katarzyna Moliner, Vicent 2016-05-10T10:43:48Z application/pdf http://hdl.handle.net/10234/159486 https://doi.org/10.3390/molecules201017789 eng eng MDPI Molecules, 2015, vol. 20, no 10 http://www.mdpi.com/1420-3049/20/10/17789/htm BORDES, Isabel, et al. Is Promiscuous CALB a Good Scaffold for Designing New Epoxidases?. Molecules, 2015, vol. 20, no 10, p. 17789-17806. 1420-3049 http://hdl.handle.net/10234/159486 http://dx.doi.org/10.3390/molecules201017789 © MDPI AG Attribution 4.0 http://creativecommons.org/licenses/by-sa/4.0/ info:eu-repo/semantics/openAccess CC-BY-SA Candida antarctica lipase B CALB epoxide hydrolase sEH reaction mechanism trans-diphenylpropene oxide enzyme promiscuity catalysis quantum cluster models info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 2016 ftunivjaumeirep https://doi.org/10.3390/molecules201017789 2022-10-11T23:05:18Z Candida Antarctica lipase B (CALB) is a well-known enzyme, especially because of its promiscuous activity. Due to its properties, CALB was widely used as a benchmark for designing new catalysts for important organic reactions. The active site of CALB is very similar to that of soluble epoxide hydrolase (sEH) formed by a nucleophile-histidine-acid catalytic triad and an oxyanion hole typical for molecular structures derived from processes of α/β hydrolases. In this work we are exploring these similarities and proposing a Ser105Asp variant of CALB as a new catalyst for epoxide hydrolysis. In particular, the hydrolysis of the trans-diphenylpropene oxide (t-DPPO) is studied by means of quantum cluster models mimicking the active site of both enzymes. Our results, based on semi-empirical and DFT calculations, suggest that mutant Ser105Asp CALB is a good protein scaffold to be used for the bio-synthesis of chiral compounds. This work was supported by the Spanish Ministerio de Economía y Competitividad for project CTQ2012-36253-C03, Universitat Jaume I (project P1•1B2014-26), Generalitat Valenciana (PROMETEOII/2014/022 and ACOMP/2014/277 projects), the Polish National Center for Science (NCN) (grant 2011/02/A/ ST4/00246, 2012–2017), the Polish Ministry of Science and Higher Education (“Iuventus Plus” program project no. 0478/IP3/2015/73, 2015-2016), and the USA’s National Institutes of Health (ref. NIH R01 GM065368). The authors acknowledge computational resources from the Servei d’Informàtica of Universitat Jaume I and from the Technical University of Lodz. Article in Journal/Newspaper Antarc* Antarctica Repositori Universitat Jaume I (Repositorio UJI) Jaume ENVELOPE(-63.750,-63.750,-65.483,-65.483) Molecules 20 10 17789 17806 |
institution |
Open Polar |
collection |
Repositori Universitat Jaume I (Repositorio UJI) |
op_collection_id |
ftunivjaumeirep |
language |
English |
topic |
Candida antarctica lipase B CALB epoxide hydrolase sEH reaction mechanism trans-diphenylpropene oxide enzyme promiscuity catalysis quantum cluster models |
spellingShingle |
Candida antarctica lipase B CALB epoxide hydrolase sEH reaction mechanism trans-diphenylpropene oxide enzyme promiscuity catalysis quantum cluster models Bordes, Isabel Recatalá, José Świderek, Katarzyna Moliner, Vicent Is Promiscuous CALB a Good Scaffold for Designing New Epoxidases? |
topic_facet |
Candida antarctica lipase B CALB epoxide hydrolase sEH reaction mechanism trans-diphenylpropene oxide enzyme promiscuity catalysis quantum cluster models |
description |
Candida Antarctica lipase B (CALB) is a well-known enzyme, especially because of its promiscuous activity. Due to its properties, CALB was widely used as a benchmark for designing new catalysts for important organic reactions. The active site of CALB is very similar to that of soluble epoxide hydrolase (sEH) formed by a nucleophile-histidine-acid catalytic triad and an oxyanion hole typical for molecular structures derived from processes of α/β hydrolases. In this work we are exploring these similarities and proposing a Ser105Asp variant of CALB as a new catalyst for epoxide hydrolysis. In particular, the hydrolysis of the trans-diphenylpropene oxide (t-DPPO) is studied by means of quantum cluster models mimicking the active site of both enzymes. Our results, based on semi-empirical and DFT calculations, suggest that mutant Ser105Asp CALB is a good protein scaffold to be used for the bio-synthesis of chiral compounds. This work was supported by the Spanish Ministerio de Economía y Competitividad for project CTQ2012-36253-C03, Universitat Jaume I (project P1•1B2014-26), Generalitat Valenciana (PROMETEOII/2014/022 and ACOMP/2014/277 projects), the Polish National Center for Science (NCN) (grant 2011/02/A/ ST4/00246, 2012–2017), the Polish Ministry of Science and Higher Education (“Iuventus Plus” program project no. 0478/IP3/2015/73, 2015-2016), and the USA’s National Institutes of Health (ref. NIH R01 GM065368). The authors acknowledge computational resources from the Servei d’Informàtica of Universitat Jaume I and from the Technical University of Lodz. |
format |
Article in Journal/Newspaper |
author |
Bordes, Isabel Recatalá, José Świderek, Katarzyna Moliner, Vicent |
author_facet |
Bordes, Isabel Recatalá, José Świderek, Katarzyna Moliner, Vicent |
author_sort |
Bordes, Isabel |
title |
Is Promiscuous CALB a Good Scaffold for Designing New Epoxidases? |
title_short |
Is Promiscuous CALB a Good Scaffold for Designing New Epoxidases? |
title_full |
Is Promiscuous CALB a Good Scaffold for Designing New Epoxidases? |
title_fullStr |
Is Promiscuous CALB a Good Scaffold for Designing New Epoxidases? |
title_full_unstemmed |
Is Promiscuous CALB a Good Scaffold for Designing New Epoxidases? |
title_sort |
is promiscuous calb a good scaffold for designing new epoxidases? |
publisher |
MDPI |
publishDate |
2016 |
url |
http://hdl.handle.net/10234/159486 https://doi.org/10.3390/molecules201017789 |
long_lat |
ENVELOPE(-63.750,-63.750,-65.483,-65.483) |
geographic |
Jaume |
geographic_facet |
Jaume |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_relation |
Molecules, 2015, vol. 20, no 10 http://www.mdpi.com/1420-3049/20/10/17789/htm BORDES, Isabel, et al. Is Promiscuous CALB a Good Scaffold for Designing New Epoxidases?. Molecules, 2015, vol. 20, no 10, p. 17789-17806. 1420-3049 http://hdl.handle.net/10234/159486 http://dx.doi.org/10.3390/molecules201017789 |
op_rights |
© MDPI AG Attribution 4.0 http://creativecommons.org/licenses/by-sa/4.0/ info:eu-repo/semantics/openAccess |
op_rightsnorm |
CC-BY-SA |
op_doi |
https://doi.org/10.3390/molecules201017789 |
container_title |
Molecules |
container_volume |
20 |
container_issue |
10 |
container_start_page |
17789 |
op_container_end_page |
17806 |
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1766266975420416000 |