Conformational Effects on the pro-S Hydrogen Abstraction Reaction in Cyclooxygenase-1: An Integrated QM/MM and MD Study

Christo Z. Christov, Alessio Lodola, Tatyana G. Karabencheva-Christova, Shunzhou Wan, Peter V. Coveney, Adrian J. Mulholland*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

18 Citations (Scopus)
25 Downloads (Pure)

Abstract

A key step in the cyclooxygenase reaction cycle of cyclooxygenase 1 (COX-1) is abstraction of the pro-S hydrogen atom of the arachidonic acid by a radical that is formed at the protein residue Tyr-385. Here we investigate this reaction step by a quantum-mechanics/molecular-mechanics approach in combination with molecular-dynamics simulations. The simulations identify the hydrogen abstraction angle as a crucial geometric determinant of the reaction, thus revealing the importance of the cyclooxygenase active site for calculating the potential energy surface of the reaction.

Original languageEnglish
Pages (from-to)L5-L7
Number of pages3
JournalBiophysical Journal
Volume104
Issue number5
DOIs
Publication statusPublished - 5 Mar 2013

Keywords

  • ACID AMIDE HYDROLASE
  • ENZYME CATALYSIS
  • DYNAMICS
  • SYNTHASE

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