Epoxide hydrolysis as a model system for understanding flux through a branched reaction scheme

Carlsson, Åsa Janfalk; Bauer, Paul; Dobritzsch, Doreen; Kamerlin, Shina Caroline Lynn; Widersten, Mikael

doi:10.1107/s2052252518003573

Cited by 5 publications

(3 citation statements)

References 38 publications

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“…The case of StEH1 thus highlights the importance of considering the energies of all steps of the reaction mechanism in order to reproduce and understand the origins of the selectivity. It should be mentioned that other computational techniques, such as EVB, QM/MM, and MD simulations, have also been used to study the mechanism and selectivity of different soluble epoxide hydrolases. ,, …”

Section: Soluble Epoxide Hydrolasementioning

confidence: 99%

Modeling Enzymatic Enantioselectivity using Quantum Chemical Methodology

et al. 2020

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The computational study of enantioselective reactions is a challenging task that requires high accuracy, as very small energy differences have to be reproduced. Quantum chemical methods, most commonly density functional theory, are today an important tool in this pursuit. This Perspective describes recent efforts in modeling asymmetric reactions in enzymes by means of the quantum chemical cluster approach. The methodology is described briefly and a number of illustrative case studies performed recently at our laboratory are presented. The reviewed enzymes are limonene epoxide hydrolase, soluble epoxide hydrolase, arylmalonate decarboxylase, phenolic acid decarboxylase, benzoylformate decarboxylase, secondary alcohol dehydrogenase, acyl transferase, and norcoclaurine synthase. The challenges encountered in each example are discussed, and the modeling lessons learned are highlighted.

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Section: Soluble Epoxide Hydrolasementioning

confidence: 99%

Modeling Enzymatic Enantioselectivity using Quantum Chemical Methodology

et al. 2020

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“…An epoxide hydrolase from Solanum tuberosum (StEH1) is a well-studied enzyme with a buried active site and a well-defined main tunnel providing access into the catalytic triad. As an attractive target for protein engineering, it has been intensively studied using both experimental [16,17,18,19,20,21,22,23] and computational methods [18,20,23,24,25,26,27]. Solanum tuberosum epoxide hydrolase belongs to the α/β-hydrolase family.…”

Section: Introductionmentioning

confidence: 99%

Exploring Solanum tuberosum Epoxide Hydrolase Internal Architecture by Water Molecules Tracking

et al. 2018

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Several different approaches are used to describe the role of protein compartments and residues in catalysis and to identify key residues suitable for the modification of the activity or selectivity of the desired enzyme. In our research, we applied a combination of molecular dynamics simulations and a water tracking approach to describe the water accessible volume of Solanum tuberosum epoxide hydrolase. Using water as a molecular probe, we were able to identify small cavities linked with the active site: (i) one made up of conserved amino acids and indispensable for the proper positioning of catalytic water and (ii) two others in which modification can potentially contribute to enzyme selectivity and activity. Additionally, we identified regions suitable for de novo tunnel design that could also modify the catalytic properties of the enzyme. The identified hot-spots extend the list of the previously targeted residues used for modification of the regioselectivity of the enzyme. Finally, we have provided an example of a simple and elegant process for the detailed description of the network of cavities and tunnels, which can be used in the planning of enzyme modifications and can be easily adapted to the study of any other protein.

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“…Notably, plant EHs are usually highly regio- and/or stereoselective [ [22] , [66] , [67] , [68] ] towards specific substrates. This issue was carefully analyzed both experimentally and theoretically in StEH1, VrEH2 and Phaseolus vulgaris PvEH3 [ [23] , [69] , [70] , [71] , [72] , [73] ]. Reports have shown that modification of the stereo- and regioselectivity of the enzymes is related to the direction of the attack of water molecules and stabilization of particular transition states [ 72 ].…”

Section: Discussionmentioning

confidence: 99%

Structure-function relationship between soluble epoxide hydrolases structure and their tunnel network

Mitusińska

Wojsa²,

Bzówka³

et al. 2022

Computational and Structural Biotechnology Journal

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Epoxide hydrolysis as a model system for understanding flux through a branched reaction scheme

Abstract: Kinetic rates and computer simulations can explain regioselectivity and stereoconfiguration in the products of enzyme-catalyzed epoxide hydrolysis.

Cited by 5 publications

References 38 publications

Modeling Enzymatic Enantioselectivity using Quantum Chemical Methodology

Modeling Enzymatic Enantioselectivity using Quantum Chemical Methodology

Exploring Solanum tuberosum Epoxide Hydrolase Internal Architecture by Water Molecules Tracking

Structure-function relationship between soluble epoxide hydrolases structure and their tunnel network

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