On the mechanism of microsomal prostaglandin E synthase type-2—A theoretical study of endoperoxide reaction with MeS

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. 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.