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Conformational Effects on thepro-SHydrogen Abstraction Reaction in Cyclooxygenase-1: An Integrated QM/MM and MD Study

Authors
Journal
Biophysical Journal
0006-3495
Publisher
Elsevier
Publication Date
Volume
104
Issue
5
Identifiers
DOI: 10.1016/j.bpj.2013.01.040
Keywords
  • Biophysical Letter
Disciplines
  • Biology
  • Mathematics
  • Physics

Abstract

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.

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