Inhibitor blocks active site of a protein kinase
Protein kinases are key enzymes of cellular regulation. Protein kinase activity - the transfer of phosphoryl groups to proteins - sets the course in cellular signal transduction and controls cellular events in higher organisms.
Because these functions are highly critical, the activity of protein kinases itself is strictly regulated in the cell. Spurious activation may result in serious diseases – overactive protein kinases were found in the majority of all human cancers.
Some protein kinases contribute to tumor progression also in the course of their normal activity: during the formation of new blood vessels, in cancer cell metastasis, or in the prevention of programmed cell death. Protein kinases, therefore, are major new targets of cancer therapy. An obstacle, however, poses the huge number (hundreds) of closely homologous human protein kinases, of which only single ones are to be inhibited selectively in order to treat diseases or to elucidate signalling pathways.
The interest of our research group is to understand the functioning as well as the cellular interactions of protein kinases, and to explore the factors that govern protein kinase inhibitor selectivity, using approaches of cell biology, structural biochemistry, and X-ray crystallography.