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

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

Author information

1
Department of Structural Biology, The State University of New York at Buffalo , Buffalo, New York 14203, United States.
2
National Biomedical Center for Advanced Electron Spin Resonance Technology, Cornell University , Ithaca, New York 14853, United States.
3
Department of Chemistry and Chemical Biology, Cornell University , Ithaca, New York 14853, United States.
4
Hauptman-Woodward Medical Research Institute , Buffalo, New York 14203, United States.

Abstract

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.

PMID:
26636181
PMCID:
PMC4707933
DOI:
10.1021/acs.biochem.5b00979
[Indexed for MEDLINE]
Free PMC Article

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