Syllabus
Mechanism of proteolysis. Classes and families of proteases.
Non-specific degradation of proteins: N-end rule, ubiquitin pathway, proteasomes and antigen presentation by MHC I molecules. Lysosomes, cathepsins B,H, D, S and L and their inhibitors. Lysosomal degradation and the MHC II system. Cathepsins in inflammation; muscular dystrophy; tumors and metastasis.
Proteases in cellular regulation: caspases and apoptosis, cyclins, their degradation and the regulation of the cell cycle. Interleukin and ICE. Prohormones and proenzymes, signal peptidases and intercellular targetting.
Proteases in homeostasis: renin-angiotensin system., blood coagulation cascade. Proteases of human pathogens: processing of viral polyproteins in picornaviruses, flaviviruses and retroviruses. Specificity, activity and inhibition of the HIV protease. Proteases of human parasites and their inhibitors: plasmepsins, proteinases from Schistosoma and Trypanosoma. Endogenous proteinase inhibitors as regulators of proteolysis. 3-D structure of proteases and their inhibitors; rational, structure-assisted drug design, combinatorial chemistry, examples of protease inhibitors as succesful drugs.
References:
Handbook of proteolytic enzymes (A.J. Barett, N. D. Rawlings and F.J. Woessner, eds.) Academic Press, New York, 1998
Annotation
The course discuss proteolysis as an important mechanism of biological regulation. The topics covered involve e.g. proteasomes and non-specific degradation of intracellular proteins, apoptosis and the regulation of cell cycle, role of proteases in neurodegeneration, proteases of viruses and other human pathogens and design of protease inhibitors as novel drugs for the treatment of cancer, Alzheimer disease and AIDS. Intended for advanced students in the master course and for the PhD students of biochemistry and biology.
Lectures - in Czech -