Dieter Brömme

Dieter Brömme  (University of British Columbia, Vancouver, Canada)  

Resume: Dieter Brömme received his doctoral degree from the University of Halle-Wittenberg (GDR) in 1983. Prior to his appointment as professor at the Faculty of Dentistry at the University of British Columbia, Vancouver and Canada Research Chair in Proteases and Diseases in 2004, Dr. Bromme was a research officer at the Biotechnology Research Institute in Montreal, Canada, a project leader at Khepri Pharmaceuticals in South San Francisco and a professor at the Mount Sinai School of Medicine in New York.His research interest is focused on mammalian lysosomal cysteine proteases where he published almost 180 research papers and book chapters.  He cloned and characterized 6 novel human papain-like cathepsins.

From protease mechanisms to mechanism-based inhibitors

Cysteine cathepsins are multifunctional proteases that are involved in extracellular matrix degradation as well as in various regulatory body functions. Among them,cathepsin K is a highly potent collagenolytic and elastolytic enzyme. Its elastase activity depends on secondary substrate binding sites and its collagenase activity requires the formation of oligomeric protease complexes in the presence of glycosaminoglycanes. We call sites involved in these interactions ectosteric sites.  Ectosteric sites are not required for the degradation of other substrates and do not affect the catalytic machinery as allosteric sites do. Thus, inhibitors binding to these sites selectively block the elastase and collagenase activity of cathepsin K without affecting its other non-matrix-degradation-related functions. The talk will discuss the mechanisms of matrix protein degradation by cathepsins and the characterization of substrate-selective inhibitors.