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Updated: Jul 3, 2026

Characterization at the Molecular Level using Robust Biochemical Approaches of a New Kinase Protein
Published on: June 30, 2019
Structural analysis of PI3-kinase isoforms: identification of residues enabling selective inhibition by small
Marketa J Zvelebil1, Michael D Waterfield, Stephen J Shuttleworth
1The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK. marketa@icr.ac.uk
Abstract:
A series of small molecule, ATP-competitive phosphoinositide 3-kinase inhibitors have been examined in homology models of the four class I isoforms, p110alpha, p110beta, p110delta and p110gamma. This analysis provided an insight into the mode of binding of these inhibitors to the hinge and to other key regions of the ATP binding site in each of the four subtypes. Significantly, residues were identified that differ between these proteins, and which help explain the isoform-selective inhibition profiles of the compounds.
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