Comparison of the 1938-bound p110α with apo p110α. The 1938-bound structure is shown in cartoon representation, whereas the apo model is shown as a superimposed red Cα trace. 1938 is shown in magenta, whereas the PRD-like helix is shown in purple. Yellow spheres mark the sites of cancer-associated mutations from the COSMIC database that are near the 1938-binding site (only mutations with >10 reports are shown). Regions showing decreased HDX-MS protection for the common helical domain mutations are in orange. PtdIns(4,5)P 2 substrate (slate) was modelled in the active state based on the structure PDB 4OVV . A region of the activation loop (thick worm representation, slate) was taken from structure PDB 7PG5 because it is disordered in the 1938-bound structure. Slate spheres represent residues important for PtdIns(4,5)P 2 recognition (K942 and R949). Chocolate spheres represent residues essential for phosphate transfer (K776, H917 and H936). A bound ATP (blue) was modelled based on structure PDB 1E8X . The ATP-binding loop is in yellow. Phosphates in PtdIns(4,5)P 2 and ATP are shown in red.
