What question did this study set out to answer?

Determine the structural basis for how the small-molecule inhibitor STI-571 selectively targets and inhibits the catalytic domain of Abelson tyrosine kinase.

September 15, 2000Science

Structural Mechanism for STI-571 Inhibition of Abelson Tyrosine Kinase

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Authors

TSThomas H. SchindlerCardiac Imaging WBWilliam G. BornmannThe University of Texas MD Anderson Cancer Center PPPatricia PellicenaQB3

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Implication

Structural analysis reveals how STI-571 binds the inactive catalytic domain in Abelson tyrosine kinase, suggesting a strategy for designing highly specific kinase inhibitors.

Key Points

Determine the structural basis for how the small-molecule inhibitor STI-571 selectively targets and inhibits the catalytic domain of Abelson tyrosine kinase.
Solved the crystal structure of the catalytic domain of Abelson tyrosine kinase complexed with a variant of STI-571.
Examined the structural conformation of the unphosphorylated activation loop in comparison to active protein kinases and inactive Src family kinases.
STI-571 binds to Abelson tyrosine kinase exclusively when the enzyme adopts an inactive conformation featuring an unphosphorylated activation loop.
The conformation of the unphosphorylated activation loop in Abelson kinase is structurally distinct from active kinases and the inactive conformation of closely related Src kinases.
Exploiting unique, kinase-specific inactive conformations enables small-molecule inhibitors to achieve both high binding affinity and high target specificity.

Cite This Study

Schindler et al. (2000) studied this question.

synapsesocial.com/papers/6a109b8b4fb650da4fffb968 https://doi.org/10.1126/science.289.5486.1938

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Implication

Structural analysis reveals how STI-571 binds the inactive catalytic domain in Abelson tyrosine kinase, suggesting a strategy for designing highly specific kinase inhibitors.

Structural Mechanism for STI-571 Inhibition of Abelson Tyrosine Kinase

Discussion

Member takes

Implication

Key Points

Cite This Study

Structural Mechanism for STI-571 Inhibition of Abelson Tyrosine Kinase

Discussion

Member takes

Implication

Key Points

Cite This Study

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