A quantum chemical study of the synthesis of prostaglandin G2 by the cyclooxygenase active site in prostaglandin endoperoxide H synthase 1

L. Mattias Blomberg, Margareta R.A. Blomberg, Per E.M. Siegbahn, Wilfred A. Van der Donk, Ah Lim Tsai

Research output: Contribution to journalArticlepeer-review

Abstract

The mechanism for prostaglandin G2 synthesis in the cyclooxygenase active site of prostaglandin H synthase has been investigated using hybrid density functional theory (B3LYP). The calculations show that the six-step radical mechanism for the transformation of arachidonic acid to prostaglandin G2 suggested by Hamberg and Samuelsson is energetically feasible. The overall driving force for the reaction starting with the arachidonic acid and the active-site tyrosyl radical is estimated to be about 37 kcal/mol, and two barriers are found to be about 15 kcal/mol, in good agreement with the experimental rate corresponding to a barrier of 14.8 kcal/mol. Competing reactions are also investigated.

Original languageEnglish (US)
Pages (from-to)3297-3308
Number of pages12
JournalJournal of Physical Chemistry B
Volume107
Issue number14
DOIs
StatePublished - Apr 10 2003

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry

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