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dc.contributorUniversitat Ramon Llull. IQS
dc.contributor.authorPlanas, Antoni (Planas Sauter)
dc.contributor.authorBiarnés Fontal, Xevi
dc.contributor.authorNieto, Joan
dc.contributor.authorRovira i Virgili, Carme
dc.date.accessioned2021-01-15T11:50:25Z
dc.date.accessioned2023-07-13T05:43:33Z
dc.date.available2021-01-15T11:50:25Z
dc.date.available2023-07-13T05:43:33Z
dc.date.issued2006-01
dc.identifier.urihttp://hdl.handle.net/20.500.14342/974
dc.description.abstractThe structure and dynamics of the enzyme-substrate complex of Bacillus 1,3–1,4-β-glucanase, one of the most active glycoside hydrolases, is investigated by means of Car-Parrinello molecular dynamics simulations (CPMD) combined with force field molecular dynamics (QM/MM CPMD). It is found that the substrate sugar ring located at the –1 subsite adopts a distorted 1S3 skew-boat conformation upon binding to the enzyme. With respect to the undistorted 4C1 chair conformation, the 1S3 skew-boat conformation is characterized by: (a) an increase of charge at the anomeric carbon (C1), (b) an increase of the distance between C1 and the leaving group, and (c) a decrease of the intraring O5-C1 distance. Therefore, our results clearly show that the distorted conformation resembles both structurally and electronically the transition state of the reaction in which the substrate acquires oxocarbenium ion character, and the glycosidic bond is partially broken. Together with analysis of the substrate conformational dynamics, it is concluded that the main determinants of substrate distortion have a structural origin. To fit into the binding pocket, it is necessary that the aglycon leaving group is oriented toward the β region, and the skew-boat conformation naturally fulfills this premise. Only when the aglycon is removed from the calculation the substrate recovers the all-chair conformation, in agreement with the recent determination of the enzyme product structure. The QM/MM protocol developed here is able to predict the conformational distortion of substrate binding in glycoside hydrolases because it accounts for polarization and charge reorganization at the –1 sugar ring. It thus provides a powerful tool to model E·S complexes for which experimental information is not yet available.eng
dc.format.extent10 p.cat
dc.language.isoengcat
dc.publisherThe American Society for Biochemistry and Molecular Biologycat
dc.relation.ispartofJournal of Biological Chemistry. Vol.281, n.3 (2006), p.1432–1441cat
dc.rights© The American Society for Biochemistry and Molecular Biology
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceRECERCAT (Dipòsit de la Recerca de Catalunya)
dc.subject.otherBacil antràciccat
dc.subject.otherGlicòsidscat
dc.subject.otherDinàmica molecularcat
dc.subject.otherEnzymescat
dc.subject.otherGlycoside hydrolasescat
dc.subject.otherMolecular dynamics simulationscat
dc.subject.otherAglyconcat
dc.titleSubstrate distortion in the Michaelis complex of Bacillus 1,3–1,4-β-glucanase: insight from first principles molecular dynamics simulationscat
dc.typeinfo:eu-repo/semantics/articlecat
dc.typeinfo:eu-repo/semantics/publishedVersioncat
dc.rights.accessLevelinfo:eu-repo/semantics/openAccess
dc.embargo.termscapcat
dc.subject.udc577
dc.identifier.doihttps://doi.org/10.1074/jbc.m507643200cat
dc.relation.projectIDinfo:eu-repo/grantAgreement/Generalitat de Catalunya/SGR/2005SGR-00036cat
dc.relation.projectIDinfo:eu-repo/grantAgreement/MCYT/PN I+D/BFU2004-06377-C02-02cat
dc.relation.projectIDinfo:eu-repo/grantAgreement/MCYT/PN I+D/FIS2005-00655cat


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