Conformational analysis of the DFG-out kinase motif and biochemical profiling of structurally validated type II inhibitors.

ABSTRACT: Structural coverage of the human kinome has been steadily increasing over time. The structures provide valuable insights into the molecular basis of kinase function and also provide a foundation for understanding the mechanisms of kinase inhibitors. There are a large number of kinase structures in the PDB for which the Asp and Phe of the DFG motif on the activation loop swap positions, resulting in the formation of a new allosteric pocket. We refer to these structures as "classical DFG-out" conformations in order to distinguish them from conformations that have also been referred to as DFG-out in the literature but that do not have a fully formed allosteric pocket. We have completed a structural analysis of almost 200 small molecule inhibitors bound to classical DFG-out conformations; we f

SUBMITTER: Vijayan RS 

PROVIDER: S-EPMC4326797 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature