Figure 4. Mechanism of ANS induced stabilization of intemediate I2.
(left) ANS binding to the allosteric site adjacent to C-helix in c-src kinase stabilizes the intermediate conformation by blocking the interactions between Lys295 and Glu310. The hydrogen bond formation between Lys295 and Glu310 is required for the locking of the C-helix in the active conformation. The sulfonate group in the ANS forms a hydrogen-bond with the Lys295 thereby locking it in its inactive conformation. (right) ANS binding also pushes the C-helix away from the ATP binding pocket. Superimposition of the crystal structures of the inactive (cyan) and active (green) states of ATP-bound c-src kinase with the ANS-bound src-kinase (orange) reveals the distinct conformation of the c-helix in presence of ANS.
