 |
 |
 |
 |
 |
 |
Protein phosphorylation is fundamental to all aspects of cell organization and behaviour. Accordingly, the human genome encodes more than 500 protein kinases, of which the majority remain to be explored for their structure and function. While all protein kinases share a conserved catalytic core, they individually contain a diverse set of structural insertions that determine their activation mechanism, substrate preferences, regulatory protein partners and subcellular localisation. Dysregulation of kinase function is a hallmark of most human cancers and increasingly recognized as a common mechanism for many other diseases involving inflammation, infection or neurodegeneration. As a result, kinase inhibitor development has been one of the major focuses of drug development during the past two decades.
The SGC aims to increase our understanding of the “unexplored” human kinome through large-scale structure determination and small molecule screening efforts. To date, the SGC has solved the catalytic domain structure of some 75 human kinases, representing about one third of all known structures (a summary of protein kinase structural biology is maintained here). The majority of our structures are solved in complex with small molecule inhibitors, including many of clinical relevance, to contribute to targeted drug development. In addition, we collaborate with many labs to develop highly selective chemical probe for protein kinases that can be used in disease models for target validation as well as to advance our basic understanding of kinase biology.