SCIENCE AT THE EDGE SEMINAR http://www.pa.msu.edu/seminars/edge 11:30 A.M., Friday, November 8, 2002 Room 1425 Biomedical and Physical Sciences Building Refreshments served at 11:15 Speaker: Michael Garavito Department of Biochemistry and Molecular Biology Michigan State University Title: The Elephant and the Blind Men: Assessing the Structure and Function of Prostaglandin endoperoxide H2 synthase Abstract: Prostaglandin endoperoxide H2 synthases (PGHSs) are a membrane bound, heme-dependent bifunctional enzymes found in mammals. Also known as cyclooxygenases or COXs, PGHSs catalyze the committed step in prostanoid synthesis via two sequential enzymatic reactions: 1) the bis-oxygenation of arachidonic acid (via the cyclooxygenase reaction) forms PGG2 and 2) reduction of PGG2 during the peroxidase reaction forms PGH2. Understanding the structure and function of the PGHS isoforms has been the focus of much recent research because both isoforms are the targets of nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin and ibuprofen. Although research on PGHSs has resulted in a vast amount of information about the pharmacology and structural biology of these enzymes, several aspects of their biochemistry and enzymology remain as mysterious as ever. The focus of this talk will be on how the study of PGHS illustrates the many of the problems and limitations facing modern structure-based design.