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Copper sites of dopamine. beta. -hydroxylase: an X-ray absorption spectroscopic study

Journal Article · · Biochemistry; (United States)
DOI:https://doi.org/10.1021/bi00415a005· OSTI ID:7186938

X-ray absorption edge and extended X-ray absorption fine structure (EXAFS) spectra are reported for the Cu(I) and Cu(II) forms of bovine dopamine ..beta..-hydroxylase and for the Cu(I) form of DBH bound either to tyramine substrate or to a multisubstrate inhibitor. A significant change in the structure of the copper sites occurs upon ascorbate-mediated reduction of Cu(II) DBH to the Cu(I) form. While the average Cu(II) site most likely consists of a square-planar array of four (N,O)-containing ligands at 1.98 A, the average Cu(I) site shows a reduction in (N,O) coordination number (from approx. 4 to approx. 2) and the addition of a S-containing ligand at 2.30 A. No change in the average Cu(I) ligand environment accompanies binding of tyramine substrate, whereas binding of a multisubstrate inhibitor, 1-(3,5-difluoro-4-hydroxybenzyl)-1H-imidazole-2(3H)-thione, causes an increase in the Cu-S coordination, consistent with inhibitor binding to the Cu(I) site through the S atom. Although excellent signal-to-noise ratio in the EXAFS spectra of ascorbate-reduced DBH facilitated analysis of outer-shell scattering for a Cu...Cu interaction, the presence of a binuclear site could not be proven or disproven due to interference from Cu...C scattering involving the carbons of imidazole ligands.

Research Organization:
Univ. of Georgia, Athens (USA)
OSTI ID:
7186938
Journal Information:
Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 27:15; ISSN BICHA
Country of Publication:
United States
Language:
English

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