Function, Structure and Topology of Protein Kinases

Protein kinases represent one of the most successful target classes for the development of new medicines. Because of their key roles in cellular signalling, kinases are stringently regulated by a large diversity of mechanisms such as post-translational modifications, interacting domains and proteins and cellular localization. The high plasticity of protein kinases has been exploited for the development of new inhibitor types such as type-II and type-I½ inhibitors targeting inactive states of the kinase catalytic domain and allosteric inhibitors that target induced binding pockets either adjacent (type-III) or distantly located (type-IV) to the kinase ATP-binding site. Here we discuss structural elements of the kinase active site, key mechanisms of kinase regulation and how these mechanisms can be exploited for the development of selective kinase inhibitors.