The Discovery of Abl Kinase ATPase Activity and Its Implications in the Development of Straightforward Assays

Abelson kinase (Abl) is an enzyme crucial in metabolic pathways, and it is a molecular target for leukemias, especially chronic myeloid leukemia. Despite extensive research on its kinase function and inhibition over the years, there is still considerable room for new discoveries regarding its mechanistic and reactive aspects. We report here, for the first time, the intrinsic ATPase activity of Abl in the absence of peptide substrates. Using quantitative one-dimensional ³¹P nuclear magnetic resonance spectroscopy, we monitored the conversion of ATP to ADP and inorganic phosphate (Pi) catalyzed by Abl. Furthermore, we demonstrated that the known kinase inhibitors imatinib and dasatinib inhibit ATPase activity. Beyond expanding the biochemical repertoire of Abl, this finding enables a straightforward, substrate-free assay for kinase inhibition, offering new perspectives on kinase catalytic plasticity and laying the groundwork for simplified screening strategies in drug discovery.