Dynamics in the p38α MAP Kinase–SB203580 Complex Observed by Liquid‐State NMR Spectroscopy
Abstract
Added flexibility: NMR data for p38α MAP kinase in a complex with the SB203580 inhibitor show intermediate exchange of residues in the binding pocket (affected residues marked in blue and red on the structure), which indicates increased flexibility compared to that of the unbound protein. Based on residual dipolar couplings, the overall solution structure of p38α is very similar to the crystal structure. Thus, the increased mobility in solution is an effect of the inhibitor that is not reflected in the crystal structure.
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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 [68]
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Molecular basis of MAP kinase regulation
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- Authors
- Honndorf, V. S., Coudevylle, N., Laufer, S., Becker, S., & Griesinger, C.
- Affiliations
- Max Planck Institute for Biophysical Chemistry (DE)
- University of Tübingen (DE)
- Corresponding author
- Griesinger, Christian
- Venue
- Angewandte Chemie International Edition
- Publisher
- Wiley
- Published
- 2008-04-21
- Volume
- 47
- Issue
- 19
- Pages
- 3548-3551
- ISSN
- 1433-7851 (ISSN-L)
- 1521-3773
- OpenAlex
- W2148255310
- Cited by
- 22
- References
- 18
- Citations by year
- 2025: 1 · 2020: 1 · 2019: 1 · 2016: 2 · 2015: 2 · 2014: 3 · 2013: 4 · 2012: 2
- FWCI
- 0.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Angewandte Chemie International Edition (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- GRO (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Chemistry › Spectroscopy › Advanced NMR Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- p38α MAP kinase, SB203580, kinase inhibitors, protein-inhibitor complex, solution structure, protein flexibility, binding pocket, residual dipolar couplings, liquid-state NMR, crystal structure comparison
- MeSH terms
- Humans, Imidazoles, Protein Conformation, Pyridines, Crystallography, X-Ray, Nuclear Magnetic Resonance, Biomolecular, Protein Kinase Inhibitors, Mitogen-Activated Protein Kinase 14
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