A series of experiments have been proposed to elucidate the mechanisms of two enzymes, dopamine Beta-monooxygenase and peptidylglycine alpha-hydroxylating monooxygenase. These enzymes play an important role in the synthesis and regulation of hormones. Many aspects in the mechanisms of these enzymes are still unresolved. We propose to trap and characterize several of the intermediates generated by the enzymes throughout the catalytic cycle, using Co(ll) complexes. These complexes will also allow us to probe the redox properties of the copper cofactors involved in these processes. Studies will be carried out on both enzymes in order to draw comparisons between the two systems.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32GM067351-01A1
Application #
6695342
Study Section
Special Emphasis Panel (ZRG1-F04 (20))
Program Officer
Marino, Pamela
Project Start
2003-09-22
Project End
2005-09-21
Budget Start
2003-09-22
Budget End
2004-09-21
Support Year
1
Fiscal Year
2003
Total Cost
$41,608
Indirect Cost
Name
University of California Berkeley
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Hess, Corinna R; Klinman, Judith P; Blackburn, Ninian J (2010) The copper centers of tyramine ?-monooxygenase and its catalytic-site methionine variants: an X-ray absorption study. J Biol Inorg Chem 15:1195-207
Hess, Corinna R; Wu, Zinian; Ng, Adora et al. (2008) Hydroxylase activity of Met471Cys tyramine beta-monooxygenase. J Am Chem Soc 130:11939-44
Hess, Corinna R; McGuirl, Michele M; Klinman, Judith P (2008) Mechanism of the insect enzyme, tyramine beta-monooxygenase, reveals differences from the mammalian enzyme, dopamine beta-monooxygenase. J Biol Chem 283:3042-9
Ghattas, Wadih; Hess, Corinna R; Iacazio, Gilles et al. (2006) Pathway for the stereocontrolled Z and E production of alpha,alpha-difluorine-substituted phenyl butenoates. J Org Chem 71:8618-21