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Science 7 May 2004:
Vol. 304. no. 5672, pp. 864 - 867
DOI: 10.1126/science.1094583
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Reports

Dioxygen Binds End-On to Mononuclear Copper in a Precatalytic Enzyme Complex

Sean T. Prigge,1,2 Betty A. Eipper,3 Richard E. Mains,3 L. Mario Amzel2*

Copper active sites play a major role in enzymatic activation of dioxygen. We trapped the copper-dioxygen complex in the enzyme peptidylglycine-alphahydroxylating monooxygenase (PHM) by freezing protein crystals that had been soaked with a slow substrate and ascorbate in the presence of oxygen. The x-ray crystal structure of this precatalytic complex, determined to 1.85-angstrom resolution, shows that oxygen binds to one of the coppers in the enzyme with an end-on geometry. Given this structure, it is likely that dioxygen is directly involved in the electron transfer and hydrogen abstraction steps of the PHM reaction. These insights may apply to other copper oxygen-activating enzymes, such as dopamine beta-monooxygenase, and to the design of biomimetic complexes.

1 Department of Microbiology and Molecular Immunology, The Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
2 Department of Biophysics and Biophysical Chemistry, Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
3 Department of Neurosciences, University of Connecticut Health Center, Farmington, CT, USA.

* To whom correspondence should be addressed. E-mail: Mario{at}neruda.med.jhmi.edu

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