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

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• 作者：Benjamin J. Orlando ; Peter P. Borbat ; Elka R. Georgieva ; Jack H. Freed ; Michael G. Malkowski
• 刊名：Biochemistry
• 出版年：2015
• 出版时间：December 22, 2015
• 年：2015
• 卷：54
• 期：50
• 页码：7309-7312
• 全文大小：220K
• ISSN：1520-4995

文摘

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.