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

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.

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Fig. 1

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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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Correspondence to Ramón Campos-Olivas.

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Campos-Olivas, R., Marenchino, M., Scapozza, L. et al. Backbone assignment of the tyrosine kinase Src catalytic domain in complex with imatinib. Biomol NMR Assign 5, 221–224 (2011). https://doi.org/10.1007/s12104-011-9304-7

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Keywords

  • Src
  • Protein tyrosine kinase
  • Kinase domain
  • Imatinib
  • TROSY
  • Deuterated protein