Document Type
Article
Publication Version
Published Version
Publication Date
9-2014
Journal or Book Title
ACS Chemical Biology
Volume
10
Issue
1
First Page
262
Last Page
268
DOI
10.1021/cb5004702
Abstract
Kinases control many aspects of cellular signaling and are therefore therapeutic targets for numerous disease states. Monitoring the conformational changes that drive activation and inactivation of the catalytic kinase core is a challenging experimental problem due to the dynamic nature of these enzymes. We apply [13C] reductive methylation to chemically introduce NMR-active nuclei into unlabeled protein kinases. The results demonstrate that solution NMR spectroscopy can be used to monitor specific changes in the chemical environment of structurally important lysines in a [13C]-methylated kinase as it shifts from the inactive to active state. This approach provides a solution based method to complement X-ray crystallographic data and can be applied to nearly any kinase, regardless of size or method of production.
Rights
This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
Copyright Owner
American Chemical Society
Copyright Date
2014
Language
en
File Format
application/pdf
Recommended Citation
Xie, Qian; Fulton, D. Bruce; and Andreotti, Amy H., "A Selective NMR Probe to Monitor the Conformational Transition from Inactive to Active Kinase" (2014). Biochemistry, Biophysics and Molecular Biology Publications. 25.
https://lib.dr.iastate.edu/bbmb_ag_pubs/25
Comments
This article is from ACS Chemical Biology 10 (2014): 262, doi:10.1021/cb5004702. Posted with permission.