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dc.contributor.authorWilkins, Ryan Scott
dc.contributor.authorLund, Bjarte Aarmo
dc.contributor.authorIsaksen, Geir Villy
dc.contributor.authorÅqvist, Johan Lennart Gösta
dc.contributor.authorBrandsdal, Bjørn Olav
dc.date.accessioned2024-01-24T14:45:00Z
dc.date.available2024-01-24T14:45:00Z
dc.date.issued2023-12-19
dc.description.abstractChorismate mutase (CM) enzymes have long served as model systems for benchmarking new methods and tools in computational chemistry. Despite the enzymes’ prominence in the literature, the extent of the roles that activation enthalpy and entropy play in catalyzing the conversion of chorismate to prephenate is still subject to debate. Knowledge of these parameters is a key piece in fully understanding the mechanism of chorismate mutases. Within this study, we utilize EVB/MD free energy perturbation calculations at a range of temperatures, allowing us to extract activation enthalpies and entropies from an Arrhenius plot of activation free energies of the reaction catalyzed by a monofunctional Bacillus subtilis CM and the promiscuous enzyme isochorismate pyruvate lyase of Pseudomonas aeruginosa. In comparison to the uncatalyzed reaction, our results show that both enzyme-catalyzed reactions exhibit a substantial reduction in activation enthalpy, while the effect on activation entropy is relatively minor, demonstrating that enzyme-catalyzed CM reactions are enthalpically driven. Furthermore, we observe that the monofunctional CM from B. subtilis more efficiently catalyzes this reaction than its promiscuous counterpart. This is supported by a structural analysis of the reaction pathway at the transition state, from which we identified key residues explaining the enthalpically driven nature of the reactions and also the difference in efficiencies between the two enzymes.en_US
dc.identifier.citationWilkins, Lund, Isaksen, Åqvist, Brandsdal. Accurate Computation of Thermodynamic Activation Parameters in the Chorismate Mutase Reaction from Empirical Valence Bond Simulations. Journal of Chemical Theory and Computation. 2023en_US
dc.identifier.cristinIDFRIDAID 2225150
dc.identifier.doi10.1021/acs.jctc.3c01105
dc.identifier.issn1549-9618
dc.identifier.issn1549-9626
dc.identifier.urihttps://hdl.handle.net/10037/32710
dc.language.isoengen_US
dc.publisherACS Publicationsen_US
dc.relation.ispartofWilkins, R.S. (2024). Mechanisms of enzyme adaptation to extreme environments: The rational design of a thermophilic chorismate mutase. (Doctoral thesis). <a href=https://hdl.handle.net/10037/32896>https://hdl.handle.net/10037/32896</a>.
dc.relation.journalJournal of Chemical Theory and Computation
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2023 The Author(s)en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)en_US
dc.titleAccurate Computation of Thermodynamic Activation Parameters in the Chorismate Mutase Reaction from Empirical Valence Bond Simulationsen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's license is described as Attribution 4.0 International (CC BY 4.0)