Protein Kinases

Protein Kinases are important regulators of cellular events. There are more than 500 protein kinases in the human genome covering most aspects of cell signalling. Many protein kinases are involved in various diseases, where faulty regulation of a kinase has damaging effects. Protein kinases are therefore major drug targets. Currently there are 13 approved drugs that target protein kinases and more than 400 drug candidates are in clinical testing.

Developing selective inhibitors for kinases poses a tremendous challenge due to the high sequence conservation of the kinase catalytic domains. An understanding of kinase structural biology and how inhibitors interact with kinases helps both to understand the processes of cell signalling and also to design selective inhibitors.

Here at the SGC we are exploring various aspects of protein kinases:

•   We determine novel 3D structures to understand kinase regulatory mechanisms.
•   We are exploring the structural features involved in ligand binding selectivity including:
•     Ligand screening to identify novel modes of binding.
•     Ligands that bind outside of the ATP pocket (type II/III ligands) which offer more possibilities to achieve selectivity (important for drug design).
•     Determination of co-crystal structures of kinases with novel, interesting or ligands with unexpected binding properties.
•   We look at the factors involved in kinase regulation including phosphorylation and binding of regulatory proteins.