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

Biomol NMR Assign. 2011 Oct;5(2):221-4. doi: 10.1007/s12104-011-9304-7. Epub 2011 Apr 27.

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 (1)H(N), (13)C(α), (13)CO, and (15)N, and sidechain (13)C(β) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzamides
  • Catalytic Domain
  • Chickens
  • Imatinib Mesylate
  • Nuclear Magnetic Resonance, Biomolecular*
  • Piperazines / chemistry*
  • Piperazines / metabolism
  • Piperazines / pharmacology
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology
  • Pyrimidines / chemistry*
  • Pyrimidines / metabolism
  • Pyrimidines / pharmacology
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • src Homology Domains
  • src-Family Kinases / chemistry*
  • src-Family Kinases / metabolism

Substances

  • Benzamides
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Recombinant Proteins
  • Imatinib Mesylate
  • src-Family Kinases