Academic Journal
Accurate Computation of Thermodynamic Activation Parameters in the Chorismate Mutase Reaction from Empirical Valence Bond Simulations
| العنوان: | Accurate Computation of Thermodynamic Activation Parameters in the Chorismate Mutase Reaction from Empirical Valence Bond Simulations |
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| المؤلفون: | Ryan Scott Wilkins, Bjarte Aarmo Lund, Geir Villy Isaksen, Johan Åqvist, Bjørn Olav Brandsdal |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Biophysics, Biochemistry, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, Information Systems not elsewhere classified, benchmarking new methods, extract activation enthalpies, activation free energies, enzymes ’ prominence, enthalpically driven nature, catalyzed reactions exhibit, thermodynamic activation parameters, chorismate mutase reaction, catalyzed cm reactions, enthalpically driven, reaction catalyzed, activation entropy, activation enthalpy, utilize evb, uncatalyzed reaction, two enzymes, transition state, substantial reduction, structural analysis, still subject, results show, relatively minor, reaction pathway, pseudomonas aeruginosa, promiscuous counterpart |
| الوصف: | Chorismate 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| Relation: | https://figshare.com/articles/journal_contribution/Accurate_Computation_of_Thermodynamic_Activation_Parameters_in_the_Chorismate_Mutase_Reaction_from_Empirical_Valence_Bond_Simulations/24866472 |
| DOI: | 10.1021/acs.jctc.3c01105.s001 |
| الاتاحة: | https://doi.org/10.1021/acs.jctc.3c01105.s001 https://figshare.com/articles/journal_contribution/Accurate_Computation_of_Thermodynamic_Activation_Parameters_in_the_Chorismate_Mutase_Reaction_from_Empirical_Valence_Bond_Simulations/24866472 |
| Rights: | CC BY-NC 4.0 |
| رقم الانضمام: | edsbas.9CB4F2D2 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1021/acs.jctc.3c01105.s001 |
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