Fig. 4. nSH2 release reduces the PIP₂–ATP distance in the kinase domain of PI3Kα. (a) In the inactive PI3Kα, the PIP₂ faces, but is distal to, the γ-phosphate group of ATP with the distance > 6 Å, much too far for the phosphoryl transfer. The position of PIP₂ in the inactive PI3Kα is obtained from the crystal structure (; 4OVV). (b) Upon nSH2 release, PIP₂ gets close to ATP through the conformational change in kinaseC, resulting in a reduced PIP₂–ATP distance of ∼2–3 Å suitable for the phosphoryl transfer. The PIP₂ binding site in the active PI3Kα is estimated by the positions of Lys^941–944 in the kinase domain.