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Theoretical Study of the Full Reaction Mechanism of Human Soluble Epoxide Hydrolase
Author(s) -
Hopmann Kathrin H.,
Himo Fahmi
Publication year - 2006
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200501519
Subject(s) - epoxide hydrolase , epoxide , mechanism (biology) , epoxide hydrolase 2 , chemistry , biochemistry , stereochemistry , combinatorial chemistry , enzyme , catalysis , philosophy , epistemology , microsome
The complete reaction mechanism of soluble epoxide hydrolase (sEH) has been investigated by using the B3LYP density functional theory method. Epoxide hydrolases catalyze the conversion of epoxides to their corresponding vicinal diols. In our theoretical study, the sEH active site is represented by quantum‐chemical models that are based on the X‐ray crystal structure of human soluble epoxide hydrolase. The trans ‐substituted epoxide (1 S ,2 S )‐β‐methylstyrene oxide has been used as a substrate in the theoretical investigation of the sEH reaction mechanism. Both the alkylation and the hydrolytic half‐reactions have been studied in detail. We present the energetics of the reaction mechanism as well as the optimized intermediates and transition‐state structures. Full potential energy curves for the reactions involving nucleophilic attack at either the benzylic or the homo‐benzylic carbon atom of (1 S ,2 S )‐β‐methylstyrene oxide have been computed. The regioselectivity of epoxide opening has been addressed for the two substrates (1 S ,2 S )‐β‐methylstyrene oxide and ( S )‐styrene oxide.