title: On the mechanism of microsomal prostaglandin E synthase type-2--a theoretical study of endoperoxide reaction with MeS(-).
abstract: The reaction pathways of deprotonation versus nucleophilic substitution involving mPGES-2 enzyme catalysis were investigated by ab initio molecular orbital theory calculations for the reaction of methylthiolate with the endoperoxide core of PGH(2) and by the combined quantum mechanical molecular mechanical methods. The calculations showed that deprotonation mechanism is energetically more favorable than the nucleophilic substitution pathway.
authors.affiliation: Discovery Research, sanofi-aventis, 1041 Route 202/206 N, Bridgewater, NJ 08807, USA. yi.li@sanofi-aventis.com
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Michael
authors.initials: M
authors.lastname: Angelastro
authors.forename: Stephen
authors.initials: S
authors.lastname: Shimshock
authors.forename: Stephan
authors.initials: S
authors.lastname: Reiling
authors.forename: Roy J
authors.initials: RJ
authors.lastname: Vaz
mesh_terms: D001665:Binding Sites; D002384:Catalysis; D003198:Computer Simulation; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D008958:Models, Molecular; D011449:Prostaglandin Endoperoxides / Q000737:chemistry*; D000071876:Prostaglandin-E Synthases
chemical_list: D011449:Prostaglandin Endoperoxides; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases