Theoretical study of the full reaction mechanism of human soluble epoxide hydrolase
2006 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 12, no 26, 6898-6909 p.Article in journal (Refereed) Published
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-methyl styrene 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.
Place, publisher, year, edition, pages
2006. Vol. 12, no 26, 6898-6909 p.
density functional calculations; enzyme catalysis; epoxide hydrolase; reaction mechanisms; regioselectivity
IdentifiersURN: urn:nbn:se:kth:diva-7169DOI: 10.1002/chem.200501519ISI: 000240387000017ScopusID: 2-s2.0-33748532821OAI: oai:DiVA.org:kth-7169DiVA: diva2:12096
QC 201008112007-05-222007-05-222010-08-11Bibliographically approved