Exploring the reversal of enantioselectivity on a Zinc-dependent Alcohol Dehydrogenase
dc.contributor.author
dc.date.accessioned
2017-04-19T07:22:55Z
dc.date.available
2017-04-19T07:22:55Z
dc.date.issued
2017-04-18
dc.identifier.issn
1477-0520
dc.identifier.uri
dc.description.abstract
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
dc.description.sponsorship
A.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)
dc.format.mimetype
application/pdf
dc.language.iso
eng
dc.publisher
Royal Society of Chemistry (RSC)
dc.relation
info:eu-repo/grantAgreement/MINECO//CTQ2014-59212-P/ES/SPIN STATE AND ENZYMATIC CATALYSIS BASED ON BOTTOM-UP COMPUTATIONAL DESIGN/
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Reproducció digital del document publicat a: http://dx.doi.org/10.1039/C7OB00482F
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Organic and Biomolecular Chemistry, 2017, vol. 15, núm. 19, p. 4122-4129
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Articles publicats (D-Q)
dc.rights
Attribution-NonCommercial 3.0 Spain
dc.rights.uri
dc.subject
dc.title
Exploring the reversal of enantioselectivity on a Zinc-dependent Alcohol Dehydrogenase
dc.type
info:eu-repo/semantics/article
dc.rights.accessRights
info:eu-repo/semantics/openAccess
dc.embargo.terms
Cap
dc.relation.projectID
info:eu-repo/grantAgreement/EC/FP7/630978/EU/Computational Exploration of Directed Evolution rules for tuning enzymatic activities/DIREVENZYME
info:eu-repo/grantAgreement/EC/H2020/679001/EU/Network models for the computational design of proficient enzymes/NetMoDEzyme
dc.type.version
info:eu-repo/semantics/publishedVersion
dc.identifier.doi
dc.contributor.funder
dc.relation.ProjectAcronym
dc.identifier.eissn
1477-0539