Pulsed Dipolar Spectroscopy Reveals That Tyrosyl Radicals Are Generated in Both Monomers of the Cyclooxygenase-2 Dimer

Biochemistry. 2015 Dec 22;54(50):7309-12. doi: 10.1021/acs.biochem.5b00979. Epub 2015 Dec 7.


Cyclooxygenases (COXs) are heme-containing sequence homodimers that utilize tyrosyl radical-based catalysis to oxygenate substrates. Tyrosyl radicals are formed from a single turnover of substrate in the peroxidase active site generating an oxy-ferryl porphyrin cation radical intermediate that subsequently gives rise to a Tyr-385 radical in the cyclooxygenase active site and a Tyr-504 radical nearby. We have utilized double-quantum coherence (DQC) spectroscopy to determine the distance distributions between Tyr-385 and Tyr-504 radicals in COX-2. The distances obtained with DQC confirm that Tyr-385 and Tyr-504 radicals were generated in each monomer and accurately match the distances measured in COX-2 crystal structures.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cyclooxygenase 2 / chemistry*
  • Dimerization
  • Models, Molecular
  • Spectrum Analysis / methods*
  • Tyrosine / chemistry*


  • Tyrosine
  • Cyclooxygenase 2