These results were generated from a cooperation between Sanofi-Aventis and the Center for Biomolecular Magnetic Resonance. We thank Matthias Dreyer for critical comments on the manuscript.
1521-3773/asset/2002_left.gif?v=1&s=ac6b0d94a94d7ce7a210002b8096b42feffc0bcf)
1521-3773/asset/2002_right.gif?v=1&s=451042aa3415ae3ad0729984d26dee1866aca82e)
Communication
NMR Characterization of Kinase p38 Dynamics in Free and Ligand-Bound Forms†
Article first published online: 22 DEC 2005
DOI: 10.1002/anie.200502770
Copyright © 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Additional Information
How to Cite
Vogtherr, M., Saxena, K., Hoelder, S., Grimme, S., Betz, M., Schieborr, U., Pescatore, B., Robin, M., Delarbre, L., Langer, T., Wendt, K. U. and Schwalbe, H. (2006), NMR Characterization of Kinase p38 Dynamics in Free and Ligand-Bound Forms. Angew. Chem. Int. Ed., 45: 993–997. doi: 10.1002/anie.200502770
- †
Publication History
- Issue published online: 23 JAN 2006
- Article first published online: 22 DEC 2005
- Manuscript Revised: 15 OCT 2005
- Manuscript Received: 5 AUG 2005
- Abstract
- Article
- References
- Cited By
Keywords:
- drug design;
- enzyme inhibitors;
- NMR spectroscopy;
- protein kinases
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).