NMR Characterization of Kinase p38 Dynamics in Free and Ligand‐Bound Forms

Abstract

In its apo state kinase p38 effects slow motions that can be detected in the NMR spectrum. One of the affected parts is the pharmacologically interesting DFG motif. Diarylurea inhibitors that bind to the DFG-out conformation lock this motif in a defined state, whereas DFG-in inhibitors that bind to the adjacent hinge region leave the flexibility of the DFG motif unaffected (see crystal structure of the complex of p38 with the inhibitor SB203580).