Detection of Ligand-induced Conformational Changes in the Activation Loop of Aurora-A Kinase by PELDOR Spectroscopy.

ABSTRACT: The structure of protein kinases has been extensively studied by protein crystallography. Conformational movement of the kinase activation loop is thought to be crucial for regulation of activity; however, in many cases the position of the activation loop in solution is unknown. Protein kinases are an important class of therapeutic target and kinase inhibitors are classified by their effect on the activation loop. Here, we report the use of pulsed electron double resonance (PELDOR) and site-directed spin labeling to monitor conformational changes through the insertion of MTSL [S-(1-oxyl-2,2,5,5-tetramethyl-2,5-dihydro-1 H-pyrrol-3-yl)methyl methanesulfonothioate] on the dynamic activation loop and a stable site on the outer surface of the enzyme. The action of different ligands such as mic

SUBMITTER: Burgess SG 

PROVIDER: S-EPMC5167317 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature