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1253159 
Journal Article 
Theoretical study of the full reaction mechanism of human soluble epoxide hydrolase 
Hopmann, KH; Himo, F 
2006 
Yes 
Chemistry: A European Journal
ISSN: 0947-6539
EISSN: 1521-3765 
WILEY-V C H VERLAG GMBH 
WEINHEIM 
12 
26 
6898-6909 
English 
16856182 
WOS:000240387000017 
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 (1S,2S)-beta-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 (1S,2S)-beta-methylstyrene oxide have been computed. The regioselectivity of epoxide opening has been addressed for the two substrates (1S,2S)-beta-methylstyrene oxide and (S)-styrene oxide.