1FPU

CRYSTAL STRUCTURE OF ABL KINASE DOMAIN IN COMPLEX WITH A SMALL MOLECULE INHIBITOR

Summary for 1FPU

• Entry DOI: 10.2210/pdb1fpu/pdb
• Descriptor: PROTO-ONCOGENE TYROSINE-PROTEIN KINASE ABL, N-[4-METHYL-3-[[4-(3-PYRIDINYL)-2-PYRIMIDINYL]AMINO]PHENYL]-3-PYRIDINECARBOXAMIDE (3 entities in total)
• Functional Keywords: kinase, kinase inhibitor, sti-571, activation loop, transferase
• Biological source: Mus musculus (house mouse)
• Cellular location: Cytoplasm, cytoskeleton: P00520
• Total number of polymer chains: 2
• Total formula weight: 68251.88

Authors

Schindler, T.,Bornmann, W.,Pellicena, P.,Miller, W.T.,Clarkson, B.,Kuriyan, J. (deposition date: 2000-08-31, release date: 2000-09-20, Last modification date: 2024-03-13)

Primary citation

Schindler, T.,Bornmann, W.,Pellicena, P.,Miller, W.T.,Clarkson, B.,Kuriyan, J.
Structural mechanism for STI-571 inhibition of abelson tyrosine kinase.
Science, 289:1938-1942, 2000

PubMed Abstract: The inadvertent activation of the Abelson tyrosine kinase (Abl) causes chronic myelogenous leukemia (CML). A small-molecule inhibitor of Abl (STI-571) is effective in the treatment of CML. We report the crystal structure of the catalytic domain of Abl, complexed to a variant of STI-571. 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 mechanisms of individual protein kinases can achieve both high affinity and high specificity.

PubMed: 10988075
DOI: 10.1126/science.289.5486.1938

Experimental method

X-RAY DIFFRACTION (2.4 Å)