4XE0

Idelalisib bound to the p110 subunit of PI3K delta

Summary for 4XE0

• Entry DOI: 10.2210/pdb4xe0/pdb
• Descriptor: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform, 5-fluoro-3-phenyl-2-[(1S)-1-(7H-purin-6-ylamino)propyl]quinazolin-4(3H)-one (3 entities in total)
• Functional Keywords: zydelig, pi3k, kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Mus musculus (Mouse)
• Cellular location: Cytoplasm : O35904
• Total number of polymer chains: 1
• Total formula weight: 108182.03

Authors

Somoza, J.R.,Villasenor, A. (deposition date: 2014-12-20, release date: 2015-02-04, Last modification date: 2023-09-27)

Primary citation

Somoza, J.R.,Koditek, D.,Villasenor, A.G.,Novikov, N.,Wong, M.H.,Liclican, A.,Xing, W.,Lagpacan, L.,Wang, R.,Schultz, B.E.,Papalia, G.A.,Samuel, D.,Lad, L.,McGrath, M.E.
Structural, Biochemical, and Biophysical Characterization of Idelalisib Binding to Phosphoinositide 3-Kinase delta.
J.Biol.Chem., 290:8439-8446, 2015

PubMed Abstract: Idelalisib (also known as GS-1101, CAL-101, IC489666, and Zydelig) is a PI3Kδ inhibitor that has recently been approved for the treatment of several hematological malignancies. Given its use in human diseases, we needed a clear picture of how idelalisib binds to and inhibits PI3Kδ. Our data show that idelalisib is a potent and selective inhibitor of the kinase activity of PI3Kδ. A kinetic characterization clearly demonstrated ATP-competitive inhibition, and several additional biochemical and biophysical assays showed that the compound binds reversibly and noncovalently to the kinase. A crystal structure of idelalisib bound to the p110δ subunit of PI3Kδ furthers our understanding of the binding interactions that confer the potency and selectivity of idelalisib.

PubMed: 25631052
DOI: 10.1074/jbc.M114.634683

Experimental method

X-RAY DIFFRACTION (2.434 Å)