Work

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

Year: 2025

Type: article

Abstract: Abelson kinase (Abl) is 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 31 P 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.

Source: ACS Omega

DOI: 10.1021/acsomega.5c08176

Authors: Diego Magno Martins, Philipe Oliveira Fernandes, Lucas Almeida Vieira, Tiago Antônio Brandão, Adolfo Henrique Moraes

Institution: Universidade Federal de Minas Gerais

Language: English

Topic: Protein Kinase Regulation and GTPase Signaling

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,935