Non-heme-metal-containing oxygenases have been shown to be involved in a large number of metabolic processes in both mammalian and bacterial systems. The broad objective of our program is to continue our analysis of the involvement of non-heme iron in the catalytic pathway of the bacterial dioxygenases, protocatechuate-3,4-dioxygenase (PCD), and catechol dioxygenase (CTD), and to carry out comparative studies with the mammalian non-heme iron monooxygenase, liver phenylalanine hydroxylase (PAH), the mammalian copper monooxygenase, dopamine-Beta-hydroxylase (DBH), and the bacterial non-heme iron monooxygenase, P. olevorans epoxidase/hydroylase (POEH). The major spectroscopic technique to be used in these studies is extended X-ray absorption fine structure (EXAFS) spectroscopy. Among the specific aims are (1) to use EXAFS to identify the nature, number, and distances of iron and copper-binding ligands; (2) to examine the interaction of active site metals with substrates, inhibitors, cofactors, and transition state analogs; (3) to draw on our experience in designing transition state analogs by examining new classes of compounds designed to mimic catalytic intermediates, and also to trap functionalities which participate in catalysis and/or are freed due to ligation alterations during the catalytic cycle. Information of the type we propose to obtain is essential to an understanding of molecular basis of non-heme metallo oxygenase catalysis and the design of specific effectors for these important enzymes.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM023474-08
Application #
3271663
Study Section
Physical Biochemistry Study Section (PB)
Project Start
1984-04-01
Project End
1988-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
8
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Georgia Institute of Technology
Department
Type
Schools of Arts and Sciences
DUNS #
097394084
City
Atlanta
State
GA
Country
United States
Zip Code
30332