NOVEL PROSTAGLANDIN SYNTHASE

描述:

DESCRIPTION: 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.