1FPU

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

1FPU の概要

• エントリーDOI: 10.2210/pdb1fpu/pdb
• 分子名称: PROTO-ONCOGENE TYROSINE-PROTEIN KINASE ABL, N-[4-METHYL-3-[[4-(3-PYRIDINYL)-2-PYRIMIDINYL]AMINO]PHENYL]-3-PYRIDINECARBOXAMIDE (3 entities in total)
• 機能のキーワード: kinase, kinase inhibitor, sti-571, activation loop, transferase
• 由来する生物種: Mus musculus (house mouse)
• 細胞内の位置: Cytoplasm, cytoskeleton: P00520
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 68251.88

構造登録者

Schindler, T.,Bornmann, W.,Pellicena, P.,Miller, W.T.,Clarkson, B.,Kuriyan, J. (登録日: 2000-08-31, 公開日: 2000-09-20, 最終更新日: 2024-03-13)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.4 Å)