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Inferential NMR/X-ray-Based Structure Determination of a Dibenzo[a,d]cycloheptenone Inhibitor–p38α MAP Kinase Complex in Solution^†

Dr. Valerie S. Honndorf

Department of NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen (Germany)

These authors contributed equally.

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Dr. Nicolas Coudevylle,

Dr. Nicolas Coudevylle

Department of NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen (Germany)

These authors contributed equally.

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Prof. Dr. Stefan Laufer,

Prof. Dr. Stefan Laufer

Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Eberhard-Karls-University, Tübingen (Germany)

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Dr. Stefan Becker,

Dr. Stefan Becker

Department of NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen (Germany)

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Prof. Dr. Christian Griesinger,

Corresponding Author

Prof. Dr. Christian Griesinger

[email protected]

Department of NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen (Germany)

Christian Griesinger, Department of NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen (Germany)

Michael Habeck, Department of Protein Evolution, Max Planck Institute for Developmental Biology, Spemannstrasse 35, 72076 Tübingen (Germany)

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Dr. Michael Habeck,

Corresponding Author

Dr. Michael Habeck

[email protected]

Department of Protein Evolution, Max Planck Institute for Developmental Biology, Spemannstrasse 35, 72076 Tübingen (Germany)

Christian Griesinger, Department of NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen (Germany)

Michael Habeck, Department of Protein Evolution, Max Planck Institute for Developmental Biology, Spemannstrasse 35, 72076 Tübingen (Germany)

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Dr. Valerie S. Honndorf,

Dr. Valerie S. Honndorf

Department of NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen (Germany)

These authors contributed equally.

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Dr. Nicolas Coudevylle,

Dr. Nicolas Coudevylle

Department of NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen (Germany)

These authors contributed equally.

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Prof. Dr. Stefan Laufer,

Prof. Dr. Stefan Laufer

Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Eberhard-Karls-University, Tübingen (Germany)

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Dr. Stefan Becker,

Dr. Stefan Becker

Department of NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen (Germany)

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Prof. Dr. Christian Griesinger,

Corresponding Author

Prof. Dr. Christian Griesinger

[email protected]

Department of NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen (Germany)

Christian Griesinger, Department of NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen (Germany)

Michael Habeck, Department of Protein Evolution, Max Planck Institute for Developmental Biology, Spemannstrasse 35, 72076 Tübingen (Germany)

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Dr. Michael Habeck,

Corresponding Author

Dr. Michael Habeck

[email protected]

Department of Protein Evolution, Max Planck Institute for Developmental Biology, Spemannstrasse 35, 72076 Tübingen (Germany)

Christian Griesinger, Department of NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen (Germany)

Michael Habeck, Department of Protein Evolution, Max Planck Institute for Developmental Biology, Spemannstrasse 35, 72076 Tübingen (Germany)

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First published: 24 January 2012

https://doi.org/10.1002/ange.201105241

Citations: 2

^†

M.H. acknowledges funding from the German Science Foundation (DFG HA 5918/1-1). C.G. thanks the Max Planck Society and the DFG (GRK 1034). We thank Thilo Stehle and Johannes Romir for providing the crystal structure and X-ray data for the p38α–1 complex.

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Graphical Abstract

Komplex(e) Probleme: Die Kristallstruktur der Mitogen-aktivierten Proteinkinase p38α im Komplex mit einem Dibenzo[a,d]cycloheptenon-Inhibitor erwies sich als unvereinbar mit NMR-spektroskopischen Daten für denselben Komplex in Lösung. Durch inferenzielle Strukturaufklärung (ISD) unter Verwendung von Randbedingungen aus Röntgenkristallographie und NMR-Spektren wurde eine Struktur ermittelt, die mit beiden Datensätzen kompatibel und der Röntgenkristallstruktur sehr ähnlich ist (siehe Bild).

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References

1E. R. Ottosen, M. D. Sorensen, F. Bjorkling, T. Skak-Nielsen, M. S. Fjording, H. Aaes, L. Binderup, J. Med. Chem. 2003, 46, 5651–5662.
10.1021/jm030851s
CAS PubMed Web of Science® Google Scholar
2L. Revesz, E. Blum, F. E. Di Padova, T. Buhl, R. Feifel, H. Gram, P. Hiestand, U. Manning, G. Rucklin, Bioorg. Med. Chem. Lett. 2004, 14, 3601–3605.
10.1016/j.bmcl.2004.03.111
CAS PubMed Web of Science® Google Scholar
3S. A. Laufer, G. M. Ahrens, S. C. Karcher, J. S. Hering, R. Niess, J. Med. Chem. 2006, 49, 7912–7915.
10.1021/jm061072p
CAS PubMed Web of Science® Google Scholar
4S. C. Koeberle, J. Romir, S. Fischer, A. Koeberle, V. Schattel, W. Albrecht, C. Grütter, O. Werz, D. Rauh, T. Stehle, S. A. Laufer, Nat. Chem. Biol. 2011, doi: 10.1038/nchembio.761 [Epub ahead of print].
Google Scholar
5V. S. Honndorf, N. Coudevylle, S. Laufer, S. Becker, C. Griesinger, Angew. Chem. 2008, 120, 3604–3607;
10.1002/ange.200705614
Google Scholar
Angew. Chem. Int. Ed. 2008, 47, 3548–3551.
10.1002/anie.200705614
CAS PubMed Web of Science® Google Scholar
6M. Vogtherr, K. Saxena, S. Hoelder, S. Grimme, M. Betz, U. Schieborr, B. Pescatore, M. Robin, L. Delarbre, T. Langer, K. U. Wendt, H. Schwalbe, Angew. Chem. 2006, 118, 1008–1012;
10.1002/ange.200502770
Google Scholar
Angew. Chem. Int. Ed. 2006, 45, 993–997.
10.1002/anie.200502770
CAS PubMed Web of Science® Google Scholar
7G. Cornilescu, J. L. Marquardt, M. Ottiger, A. Bax, J. Am. Chem. Soc. 1998, 120, 6836–6837.
10.1021/ja9812610
CAS Web of Science® Google Scholar
8W. Rieping, M. Habeck, M. Nilges, Science 2005, 309, 303–306.
10.1126/science.1110428
CAS PubMed Web of Science® Google Scholar
9W. Rieping, M. Nilges, M. Habeck, Bioinformatics 2008, 24, 1104–1105.
10.1093/bioinformatics/btn062
CAS PubMed Web of Science® Google Scholar
10D. M. Lemaster, F. M. Richards, Biochemistry 1988, 27, 142–150.
10.1021/bi00401a022
CAS PubMed Web of Science® Google Scholar
11M. Bukhtiyarova, K. Northrop, X. Chai, D. Casper, M. Karpusas, E. Springman, Protein Expression Purif. 2004, 37, 154–161.
10.1016/j.pep.2004.05.017
CAS PubMed Web of Science® Google Scholar
12F. Delaglio, S. Grzesiek, G. W. Vuister, G. Zhu, J. Pfeifer, A. Bax, J. Biomol. NMR 1995, 6, 277–293.
10.1007/BF00197809
CAS PubMed Web of Science® Google Scholar
13R. Keller, The Computer Aided Resonance Assignment Tutorial, Cantina Verlag, Goldau, 2004.
Google Scholar
14M. Vogtherr, K. Saxena, S. Grimme, M. Betz, U. Schieborr, B. Pescatore, T. Langer, H. Schwalbe, J. Biomol. NMR 2005, 32, 175.
10.1007/s10858-005-2449-x
CAS PubMed Web of Science® Google Scholar

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Volume124, Issue10

March 5, 2012

Pages 2409-2412

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Inferential NMR/X-ray-Based Structure Determination of a Dibenzo[a,d]cycloheptenone Inhibitor–p38α MAP Kinase Complex in Solution^†

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Inferential NMR/X-ray-Based Structure Determination of a Dibenzo[a,d]cycloheptenone Inhibitor–p38α MAP Kinase Complex in Solution†

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Inferential NMR/X-ray-Based Structure Determination of a Dibenzo[a,d]cycloheptenone Inhibitor–p38α MAP Kinase Complex in Solution^†