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.

Comments

This article is from ACS Chemical Biology 10 (2014): 262, doi:10.1021/cb5004702. Posted with permission.

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

Language

en

File Format

application/pdf

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