4PS8

Structure of PI3K gamma in complex with N-[6-(5,6-dimethoxypyridin-3-yl)-1,3-benzothiazol-2-yl]acetamide

Summary for 4PS8

• Entry DOI: 10.2210/pdb4ps8/pdb
• Related: 4PS3 4PS7
• Descriptor: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform, N-[6-(5,6-dimethoxypyridin-3-yl)-1,3-benzothiazol-2-yl]acetamide (3 entities in total)
• Functional Keywords: serine/threonine protein kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : P48736
• Total number of polymer chains: 1
• Total formula weight: 111085.54

Authors

Griffith, J.P. (deposition date: 2014-03-06, release date: 2014-05-14, Last modification date: 2024-02-28)

Primary citation

Collier, P.N.,Martinez-Botella, G.,Cornebise, M.,Cottrell, K.M.,Doran, J.D.,Griffith, J.P.,Mahajan, S.,Maltais, F.,Moody, C.S.,Huck, E.P.,Wang, T.,Aronov, A.M.
Structural Basis for Isoform Selectivity in a Class of Benzothiazole Inhibitors of Phosphoinositide 3-Kinase gamma.
J.Med.Chem., 58:517-521, 2015

PubMed Abstract: Phosphoinositide 3-kinase γ (PI3Kγ) is an attractive target to potentially treat a range of disease states. Herein, we describe the evolution of a reported phenylthiazole pan-PI3K inhibitor into a family of potent and selective benzothiazole inhibitors. Using X-ray crystallography, we discovered that compound 22 occupies a previously unreported hydrophobic binding cleft adjacent to the ATP binding site of PI3Kγ, and achieves its selectivity by exploiting natural sequence differences among PI3K isoforms in this region.

PubMed: 24754609
DOI: 10.1021/jm500362j

Experimental method

X-RAY DIFFRACTION (2.99 Å)