Exploring the reversal of enantioselectivity on a Zinc-dependent Alcohol Dehydrogenase

Alcohol Dehydrogenase (ADH) enzymes catalyse the reversible reduction of prochiral ketones to the corresponding alcohols. These enzymes present two differently shaped active site pockets, which dictate their substrate scope and selectivity. In this study, we computationally evaluate the effect of tw...

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Detalhes bibliográficos
Autores: Maria Solano, Miguel A., Romero Rivera, Adrian, Osuna Oliveras, Sílvia
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10256/13862
Acesso em linha:http://hdl.handle.net/10256/13862
Access Level:acceso abierto
Palavra-chave:Enzims
Enzymes
Catàlisi
Catalysis
Dinàmica molecular
Molecular dynamics
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spelling Exploring the reversal of enantioselectivity on a Zinc-dependent Alcohol DehydrogenaseMaria Solano, Miguel A.Romero Rivera, AdrianOsuna Oliveras, SílviaEnzimsEnzymesCatàlisiCatalysisDinàmica molecularMolecular dynamicsAlcohol Dehydrogenase (ADH) enzymes catalyse the reversible reduction of prochiral ketones to the corresponding alcohols. These enzymes present two differently shaped active site pockets, which dictate their substrate scope and selectivity. In this study, we computationally evaluate the effect of two commonly reported active site mutations (I86A, and W110T) on a secondary alcohol dehydrogenase from Thermoanaerobacter brockii (TbSADH) through Molecular Dynamics simulations. Our results indicate that the introduced mutations induce dramatic changes on the shape of the active site, but most importantly they impact the substrate-enzyme interactions. We demonstrate that the combination of Molecular Dynamics simulations with the tools POVME and NCIplot correspond to a powerful strategy for rationalising and engineering the stereoselectivity of ADH variantsA.R.R. thanks the Generalitat de Catalunya for PhD fellowship (2015-FI-B-00165), M.A.M.S is grateful to the Spanish MINECO for PhD fellowship (BES-2015-074964). S.O. thanks the Spanish MINECO for project CTQ2014-59212-P, Ramón y Cajal contract (RYC-2014-16846), the European Community for CIG project (PCIG14-GA-2013-630978), and the funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (ERC-2015-StG-679001)Royal Society of Chemistry (RSC)Ministerio de Economía y Competitividad (Espanya)2017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10256/13862Organic and Biomolecular Chemistry, 2017, vol. 15, núm. 19, p. 4122-4129Articles publicats (D-Q)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)Inglésinfo:eu-repo/semantics/altIdentifier/doi/10.1039/C7OB00482Finfo:eu-repo/semantics/altIdentifier/issn/1477-0520info:eu-repo/semantics/altIdentifier/eissn/1477-0539info:eu-repo/grantAgreement/MINECO//CTQ2014-59212-Pinfo:eu-repo/grantAgreement/EC/FP7/630978info:eu-repo/grantAgreement/EC/H2020/679001Attribution-NonCommercial 3.0 Spainhttp://creativecommons.org/licenses/by-nc/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:10256/138622026-05-29T05:05:01Z
dc.title.none.fl_str_mv Exploring the reversal of enantioselectivity on a Zinc-dependent Alcohol Dehydrogenase
title Exploring the reversal of enantioselectivity on a Zinc-dependent Alcohol Dehydrogenase
spellingShingle Exploring the reversal of enantioselectivity on a Zinc-dependent Alcohol Dehydrogenase
Maria Solano, Miguel A.
Enzims
Enzymes
Catàlisi
Catalysis
Dinàmica molecular
Molecular dynamics
title_short Exploring the reversal of enantioselectivity on a Zinc-dependent Alcohol Dehydrogenase
title_full Exploring the reversal of enantioselectivity on a Zinc-dependent Alcohol Dehydrogenase
title_fullStr Exploring the reversal of enantioselectivity on a Zinc-dependent Alcohol Dehydrogenase
title_full_unstemmed Exploring the reversal of enantioselectivity on a Zinc-dependent Alcohol Dehydrogenase
title_sort Exploring the reversal of enantioselectivity on a Zinc-dependent Alcohol Dehydrogenase
dc.creator.none.fl_str_mv Maria Solano, Miguel A.
Romero Rivera, Adrian
Osuna Oliveras, Sílvia
author Maria Solano, Miguel A.
author_facet Maria Solano, Miguel A.
Romero Rivera, Adrian
Osuna Oliveras, Sílvia
author_role author
author2 Romero Rivera, Adrian
Osuna Oliveras, Sílvia
author2_role author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (Espanya)
dc.subject.none.fl_str_mv Enzims
Enzymes
Catàlisi
Catalysis
Dinàmica molecular
Molecular dynamics
topic Enzims
Enzymes
Catàlisi
Catalysis
Dinàmica molecular
Molecular dynamics
description Alcohol Dehydrogenase (ADH) enzymes catalyse the reversible reduction of prochiral ketones to the corresponding alcohols. These enzymes present two differently shaped active site pockets, which dictate their substrate scope and selectivity. In this study, we computationally evaluate the effect of two commonly reported active site mutations (I86A, and W110T) on a secondary alcohol dehydrogenase from Thermoanaerobacter brockii (TbSADH) through Molecular Dynamics simulations. Our results indicate that the introduced mutations induce dramatic changes on the shape of the active site, but most importantly they impact the substrate-enzyme interactions. We demonstrate that the combination of Molecular Dynamics simulations with the tools POVME and NCIplot correspond to a powerful strategy for rationalising and engineering the stereoselectivity of ADH variants
publishDate 2017
dc.date.none.fl_str_mv 2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10256/13862
url http://hdl.handle.net/10256/13862
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1039/C7OB00482F
info:eu-repo/semantics/altIdentifier/issn/1477-0520
info:eu-repo/semantics/altIdentifier/eissn/1477-0539
info:eu-repo/grantAgreement/MINECO//CTQ2014-59212-P
info:eu-repo/grantAgreement/EC/FP7/630978
info:eu-repo/grantAgreement/EC/H2020/679001
dc.rights.none.fl_str_mv Attribution-NonCommercial 3.0 Spain
http://creativecommons.org/licenses/by-nc/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NonCommercial 3.0 Spain
http://creativecommons.org/licenses/by-nc/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Royal Society of Chemistry (RSC)
publisher.none.fl_str_mv Royal Society of Chemistry (RSC)
dc.source.none.fl_str_mv Organic and Biomolecular Chemistry, 2017, vol. 15, núm. 19, p. 4122-4129
Articles publicats (D-Q)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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