These authors contributed equally.
Inferential NMR/X-ray-Based Structure Determination of a Dibenzo[a,d]cycloheptenone Inhibitor–p38α MAP Kinase Complex in Solution†
Article first published online: 24 JAN 2012
Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Angewandte Chemie International Edition
Volume 51, Issue 10, pages 2359–2362, March 5, 2012
How to Cite
Honndorf, V. S., Coudevylle, N., Laufer, S., Becker, S., Griesinger, C. and Habeck, M. (2012), Inferential NMR/X-ray-Based Structure Determination of a Dibenzo[a,d]cycloheptenone Inhibitor–p38α MAP Kinase Complex in Solution. Angew. Chem. Int. Ed., 51: 2359–2362. doi: 10.1002/anie.201105241
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.
- Issue published online: 1 MAR 2012
- Article first published online: 24 JAN 2012
- Manuscript Revised: 23 DEC 2011
- Manuscript Received: 26 JUL 2011
- German Science Foundation. Grant Number: HA 5918/1-1
- Max Planck Society
- DFG. Grant Number: GRK 1034
- NMR spectroscopy;
- structure elucidation;
- X-ray diffraction
Complex problem: The crystal structure of p38α mitogen-activated protein kinase in complex with a dibenzo[a,d]cycloheptenone inhibitor was found to be incompatible with NMR data of the same complex in solution. By using inferential structure determination (ISD) with restraints from X-ray crystallography and NMR spectra, a structure that is compatible with both data sets and very close to the X-ray crystal structure was generated (see picture).