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Influence of Water and Enzyme on the Post-Transition State Bifurcation of NgnD-Catalyzed Ambimodal [6+4]/[4+2] Cycloaddition
- Source :
- Journal of the American Chemical Society. 143(49)
- Publication Year :
- 2021
-
Abstract
- The enzyme NgnD catalyzes an ambimodal cycloaddition that bifurcates to [6+4]- and [4+2]-adducts. Both products have been isolated in experiments, but it remains unknown how enzyme and water influence the bifurcation selectivity at the femtosecond time scale. Here, we study the impact of water and enzyme on the post-transition state bifurcation of NgnD-catalyzed [6+4]/[4+2] cycloaddition by integrating quantum mechanics/molecular mechanics quasiclassical dynamics simulations and biochemical assays. The ratio of [6+4]/[4+2] products significantly differs in the gas phase, water, and enzyme. Biochemical assays were employed to validate computational predictions. The study informs how water and enzyme affect the bifurcation selectivity through perturbation of the reaction dynamics in the femtosecond time scale, revealing the fundamental roles of condensed media in dynamically controlling the chemical selectivity for biosynthetic reactions.
- Subjects :
- Molecular Dynamics Simulation
Biochemistry
Molecular mechanics
Catalysis
Nocardia
Lactones
Colloid and Surface Chemistry
Bacterial Proteins
Computational chemistry
Catalytic Domain
Carbon-Carbon Lyases
Bifurcation
Density Functional Theory
chemistry.chemical_classification
Cycloaddition Reaction
Chemistry
Water
General Chemistry
Cycloaddition
Enzyme
Models, Chemical
Reaction dynamics
Femtosecond
Biocatalysis
Selectivity
Protein Binding
Subjects
Details
- ISSN :
- 15205126
- Volume :
- 143
- Issue :
- 49
- Database :
- OpenAIRE
- Journal :
- Journal of the American Chemical Society
- Accession number :
- edsair.doi.dedup.....7f7d185642aacbfe841841599e317c77