Structural mechanism for STI-571 inhibition of abelson tyrosine kinase.

@article{Schindler2000StructuralMF,
  title={Structural mechanism for STI-571 inhibition of abelson tyrosine kinase.},
  author={Thomas E. Schindler and William G. Bornmann and Patricia Pellicena and W. Todd Miller and Bayard Clarkson and John Kuriyan},
  journal={Science},
  year={2000},
  volume={289 5486},
  pages={
          1938-42
        }
}
The inadvertent activation of the Abelson tyrosine kinase (Abl) causes chronic myelogenous leukemia (CML. [...] Key Result Critical to the binding of STI-571 is the adoption by the kinase of an inactive conformation, in which a centrally located "activation loop" is not phosphorylated. The conformation of this loop is distinct from that in active protein kinases, as well as in the inactive form of the closely related Src kinases. These results suggest that compounds that exploit the distinctive inactivation…Expand
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  • Biology, Medicine
  • Biochemical and biophysical research communications
  • 2003
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Functional studies coupled with structural analysis define a myristoyl/phosphotyrosine switch in c-Abl that regulates docking and accessibility of the SH2 domain and provides new insights into the mechanism of action of STI-571. Expand
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