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dc.creatorLee, Wook
dc.creatorVojcic, Ljubica
dc.creatorDespotovic, Dragana
dc.creatorProdanović, Radivoje
dc.creatorMaurer, Karl-Heinz
dc.creatorSchwaneberg, Ulrich
dc.creatorZacharias, Martin
dc.date.accessioned2018-11-22T00:15:48Z
dc.date.available2018-11-22T00:15:48Z
dc.date.issued2010
dc.identifier.issn1432-881X
dc.identifier.urihttp://cherry.chem.bg.ac.rs/handle/123456789/1039
dc.description.abstractThe perhydrolysis reaction in hydrolases is an important example of catalytic promiscuity and has many potential industrial applications. The mechanisms of perhydrolase activity of a subtilisin Carlsberg mutant and of an aryl-esterase mutant have been investigated using classical molecular dynamics simulations of the second tetrahedral intermediate (TI) state. The simulations demonstrated that hydrogen bonding between the second TI of the perhydrolysis reaction is possible in the mutants but not wild type. The stabilization by hydrogen bonds was specific for the perhydrolysis intermediate and either no hydrogen bonding or only weakened hydrogen bonding to the second TI state of the hydrolysis reaction was observed. Furthermore, a significant hindrance to the formation of the catalytically important hydrogen bond between His64 and Ser221 in the catalytic triad by competing hydrogen bonds was found for the subtilisin mutant but not wild type enzyme in case of the hydrolysis intermediate. The opposite was observed in case of the perhydrolysis intermediate. The result offers a qualitative explanation for the overall reduced hydrolysis activity of the subtilisin mutant. In addition, the simulations also explain qualitatively the perhydrolysis activity of the enzyme variants and may be helpful for designing enzyme mutants with further improved perhydrolysis activity.en
dc.publisherSpringer, New York
dc.relationCLAMV (Computer Laboratories for Animation, Modeling and Visualization) at Jacobs University Bremen
dc.relationEMSL (Environmental Molecular Science Laboratories) at the PNNL (Pacific Northwest National Laboratories)
dc.rightsrestrictedAccess
dc.sourceTheoretical Chemistry Accounts
dc.subjectMolecular simulationen
dc.subjectEnzyme promiscuityen
dc.subjectPerhydrolysis catalysisen
dc.subjectIntermediate stabilizationen
dc.titleRationalizing perhydrolase activity of aryl-esterase and subtilisin Carlsberg mutants by molecular dynamics simulations of the second tetrahedral intermediate stateen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractПродановић, Радивоје; Маурер, Карл-Хеинз; Зацхариас, Мартин; Сцхwанеберг, Улрицх; Војциц, Љубица; Лее, Wоок; Деспотовиц, Драгана;
dc.citation.volume125
dc.citation.issue3-6
dc.citation.spage375
dc.citation.epage386
dc.identifier.wos000273363300024
dc.identifier.doi10.1007/s00214-009-0611-3
dc.citation.other125(3-6): 375-386
dc.citation.rankM22
dc.type.versionpublishedVersionen
dc.identifier.scopus2-s2.0-77949262410
dc.identifier.rcubKon_2039


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