Fig. 2: Structural basis for PI3KC2α inhibition by PITCOINs.
From: Development of selective inhibitors of phosphatidylinositol 3-kinase C2α
a, Surface representation of the overall structure of apo PI3KC2αcore. The N- and C-lobes of the kinase domain are highlighted in cyan and blue, respectively. Inset, close-up view of the ATP-binding pocket. The adenine-binding pocket, affinity pocket and specific pocket are indicated by dashed circles. Key residues are shown by stick representation. Protein Data Bank (PDB) code: 7BI4. b, PI3KC2αcore in complex with PITCOIN3. The N-phenylmethanesulfonamide on the 4′ position of the thiazole moiety is rotated by 180° compared to the conformation in PITCOIN2. c, Schematic representation of interactions between PITCOIN3 and PI3KC2α. Hydrophobic interactions are shown as orange eyelashes. A unique hydrogen bond is shown as a green dashed line with the distance between the donor and acceptor atoms indicated. Hydrogen atoms were omitted for clarity. The phenyl sulfonamide group displays hydrophobic interactions with P1188 and E1131.
