Work

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

Year: 2015

Type: article

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.

Source: Biochemistry

DOI: 10.1021/acs.biochem.5b00979

Authors: Benjamin J. Orlando, Peter P. Borbat, Elka R. Georgieva, Jack H. Freed, Michael G. Malkowski

Institutions: University at Buffalo, State University of New York, Cornell University, Hauptman-Woodward Medical Research Institute

Language: English

Topic: Metal-Catalyzed Oxygenation Mechanisms

Subfield: Inorganic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funders: National Institute of General Medical Sciences, National Institute of Biomedical Imaging and Bioengineering