The human prostaglandin synthases, cyclooxygenase-1 and -2, are the targets of aspirin and other non-steroidal anti-inflammatory drugs. These two enzymes, which share 65% of sequence identity, are subject to intensive study in terms of their structure-function and their mechanism of catalysis and inhibition. Certain corals contain large amounts of prostaglandins (2-3% of dry weight). In a previous FRICA sponsored collaboration, Dr. Samel identified the biosynthetic pathway of cyclooxygenase in an arctic coral and discovered important differences in the catalytic activities of the coral PH synthase from the mammalian enzymes. The investigators have now obtained the partial cDNA clones of the of the coral PG synthase from the arctic as well as Caribbean corals that contain high prostaglandin contents. These cDNAs show about 50% amino acid identity to the mammalian enzymes. In the present research proposal, the investigators will clone the full length null cDNAs and express these enzymes in prokaryotes as well as in eukaryotes. These enzymes will be characterized and compared to the properties of the mammalian cycloooxygenases. It is expected that a comparison will provide valuable insights into the structure-function of the human prostaglandin synthases.

Agency
National Institute of Health (NIH)
Institute
Fogarty International Center (FIC)
Type
Small Research Grants (R03)
Project #
5R03TW000404-05
Application #
6078345
Study Section
International and Cooperative Projects 1 Study Section (ICP)
Program Officer
Michels, Kathleen M
Project Start
1998-09-30
Project End
2001-09-29
Budget Start
1999-09-30
Budget End
2000-09-29
Support Year
5
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Pharmacology
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212