NMR Characterization of Kinase p38 Dynamics in Free and Ligand‐Bound Forms
Abstract
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).
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NMR studies focused on the DFG in/out loop equilibrium and the hinge region show that these regions change dynamics upon ligand (inhibitor) binding.
“A number of NMR studies focused on the DFG in/out loop equilibrium as well as the hinge region, showing that these regions change dynamics upon ligand (inhibitor) binding.67,68”
From Molecular basis of MAP kinase regulation (2013) · cites this paper as [67]
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- Authors
- Vogtherr, M., Saxena, K., Hoelder, S., Grimme, S., Betz, M., Schieborr, U., Pescatore, B., Robin, M., Delarbre, L., Langer, T., Wendt, K. U., & Schwalbe, H.
- Affiliations
- Goethe University Frankfurt (DE)
- Sanofi (Germany) (DE)
- Sanofi (France) (FR)
- Venue
- Angewandte Chemie International Edition
- Publisher
- Wiley
- Published
- 2006-01-23
- Volume
- 45
- Issue
- 6
- Pages
- 993-997
- ISSN
- 1433-7851 (ISSN-L)
- 1521-3773
- OpenAlex
- W2139901651
- Cited by
- 145
- References
- 27
- Citations by year
- 2025: 3 · 2024: 5 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 3 · 2019: 7 · 2018: 10 · 2017: 7 · 2016: 10 · 2015: 10 · 2014: 7 · 2013: 13 · 2012: 14
- FWCI
- 2.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Angewandte Chemie International Edition (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Chemistry › Spectroscopy › Advanced NMR Techniques and Applications
- Keywords
- p38 MAPK, DFG motif, SB203580, DFG-out conformation, hinge region, ligand binding, protein flexibility, slow motion
- MeSH terms
- Animals, Dimethyl Sulfoxide, Enzyme Inhibitors, Ligands, Models, Molecular, Magnetic Resonance Spectroscopy, Phenylalanine, Plasmids, Drug Design, Crystallography, X-Ray, p38 Mitogen-Activated Protein Kinases, Mice
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