The enzyme orotidine-5'-monophosphate decarboxylase (ODCase) is involved in the biosynthesis of nucleic acid building blocks and thus represents a potential target for development of anti-tumor drugs. Developing a clear understanding of the fundamental mechanisms of key enzymes has already proven an important contribution to the discovery of new drug therapies. The goal of the proposed research is to understand how the enzyme catalyzes the conversion of the substrate orotidine-5'- monophosphate (OMP) to product uridine-5'-monophosphate (UMP) and to probe the positioning of amino acid residues in the active site of the enzyme. Substrate analogs will be synthesized and studied. NMR spectroscopy will be used to investigate substrate analog-enzyme complexes to probe the structural change of the substrate upon binding in the active site. Chemical method and site-directed mutagenesis will be used to determine the role of active-site residues. The proposed work will be carried out in collaboration with Professor Susan M. Miller at the Department of Pharmaceutical Chemistry, University of California at San Francisco.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR011805-05
Application #
6354308
Study Section
Project Start
2000-09-30
Project End
2002-09-29
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
5
Fiscal Year
2000
Total Cost
$294,097
Indirect Cost
Name
San Francisco State University
Department
Type
DUNS #
942514985
City
San Francisco
State
CA
Country
United States
Zip Code
94132
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