A selective NMR probe to monitor the conformational transition from inactive to active kinase.
Related Articles A selective NMR probe to monitor the conformational transition from inactive to active kinase.
ACS Chem Biol. 2014 Sep 23;
Authors: Xie Q, Fulton DB, Andreotti AH
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.
PMID: 25248068 [PubMed - as supplied by publisher]
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