Abelson tyrosine kinase fusion protein ATP-binding site (within BCR–ABL1) (ABL1 ATP-binding site (within BCR–ABL1), often referenced as part of BCR–ABL1 or BCR–ABL)

The ATP-binding site of BCR–ABL1 is formed at the interface of the protein’s kinase domain, specifically between the activation loop (A-loop) and the phosphate-binding loop (P-loop). Binding of ATP to this pocket enables the BCR–ABL1 fusion protein to phosphorylate tyrosine residues on substrate proteins, driving constitutive proliferation and anti-apoptotic survival signals in leukemic cells. Tyrosine kinase inhibitors (TKIs) developed for CML act by competitively occupying the ATP-binding site, effectively shutting down aberrant downstream signaling. Mutations within this site, notably T315I, alter drug binding and create therapeutic challenges. The ATP-binding site’s structural dynamics and interactions underlie both CML pathogenesis and TKI-based therapeutic strategy.

Other names

BCR–ABL1 kinase active siteBCR–ABL tyrosine kinase ATP pocketBCR–ABL1 ATP pocketBCR–ABL kinase domain ATP-binding pocketAbl domain ATP-binding siteBCR–ABL1 KD active site

Competitive inhibition: TKIs bind the ATP-binding site, preventing ATP from binding and thereby blocking phosphorylation of substrates. Allosteric inhibition (for some drugs like asciminib): binds a distant site to modulate ATP site conformation, not direct competition.