This year, the Otto Krayer Award in Pharmacology was given to Paul F. Hollenberg PhD, Emeritus Professor at the University of Michigan Medical School. While this award recognizes outstanding scientific career contributions to pharmacology, its also highlights exemplary personal qualities including commitment to teaching, guidance and support of younger scientists, in accord with those exemplified by Otto Krayer himself. Dr. Hollenberg has been the author of over 210 peer reviewed publications, has been an active member of ASPET, having served as president and treasurer on separate occasions, and has helped mentor over 50 students, post-docs and junior faculty over his more than four-decade long career!

His talk, held Monday April 23rd in the San Diego Convention Center was entitled “Active Site Structures and Catalytic Mechanisms of Drug Metabolizing Cytochrome P450s”. For those of us not too familiar with Cytochrome P450s, they are a super-family of enzymes expressed in nearly every tissue and cell in the body, and catalyze the rate limiting step for a large variety of drugs. They are also polymorphically expressed, meaning not every person will respond the same way to drugs metabolized by these enzymes, and can recognize many different substrates ultimately leading to the production of a variety of downstream products.

His talk focused on a specific property of these enzymes, called mechanism-based inhibition or “suicide inhibition”, an irreversible form of enzyme inhibition that occurs when an enzyme binds a substrate analogue and form an irreversible complex that ultimately “kills” the enzyme and precludes further participation in the reaction. His research used this mechanism to identify residues involved in substrate specificity to determine 3-D structures of P450s in their catalytically active conformations. This knowledge was subsequently used to investigate the relationship between structure and function, including research into the active site on CYP2B6 in relation to the bioactivation of the drug Clopidogrel, commonly known as Plavix, and inhibitor of platelet aggregation.

In my humble opinion, this was a truly inspiring lecture to have listened to, and while I have not yet had a chance to chat with Dr. Hollenberg at this meeting, it seems he has had a positive impact on the careers of many young scientists, and truly exemplifies the values of the Otto Krayer award.