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Biomolecular NMR Assignments

, Volume 5, Issue 2, pp 221–224 | Cite as

Backbone assignment of the tyrosine kinase Src catalytic domain in complex with imatinib

  • Ramón Campos-OlivasEmail author
  • Marco Marenchino
  • Leonardo Scapozza
  • Francesco L. Gervasio
Article

Abstract

The Src tyrosine kinase is the paradigm of an oncogenic kinase, and of regulation by intramolecular inhibitory interactions, as well as an important anticancer target due to its roles in cell proliferation and metastasis. The assignment of backbone 1HN, 13Cα, 13CO, and 15N, and sidechain 13Cβ resonances of the catalytic domain of Src (283 residues) in complex with the anticancer drug Imatinib is reported here. Consistent with previous X-ray studies of the same complex, most signals from the activation loop are not detected, indicating that, even in the presence of the drug, it probably adopts highly heterogeneous conformations in intermediate exchange. For the rest of the polypeptide backbone, assignments have been completed for ~88% of residues, with only a few solvent-exposed amides remaining unassigned.

Keywords

Src Protein tyrosine kinase Kinase domain Imatinib TROSY Deuterated protein 

Notes

Acknowledgments

This work was funded in part by Ministerio de Ciencia e Innovación of Spain grant BIO2010-20166 (FLG), and Comunidad Autónoma de Madrid grant BIPEDD-CM (RCO). Access to the 800 MHz spectrometer of the Laboratorio de RMN de Barcelona was co-financed by a grant from Programa de Acesso a ICTS from the MICINN, Spain.

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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Ramón Campos-Olivas
    • 1
    Email author
  • Marco Marenchino
    • 1
  • Leonardo Scapozza
    • 3
  • Francesco L. Gervasio
    • 2
  1. 1.Spectroscopy and NMR UnitStructural and Computational Biology Programme, Spanish National Cancer Center (CNIO)MadridSpain
  2. 2.Computational Biophysics GroupStructural and Computational Biology Programme, Spanish National Cancer Center (CNIO)MadridSpain
  3. 3.Pharmaceutical Biochemistry, School of Pharmaceutical SciencesUniversity of GenevaGeneve 4Switzerland

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