Figure 3. Comparison of the catalytic modules of SOS and RasGRP1.
(A) Structures of SOScat in the inactive state (PDB ID:2II0) (left) and active state (PDB ID: 1NVV) (right) bound to Ras (orange) at the active and allosteric sites are shown. The switch 1 and switch 2 elements of Ras are shown in purple. (B) The architecture of the catalytic module of RasGRP1 is similar to that of SOS, indicating that active site Ras will bind to at a similar location in the Cdc25 domain. (C) The helical hairpins of inactive SOS (purple), active SOS (yellow) and RasGRP1 (green) are shown with the core of the RasGRP1 Cdc25 domain (gray) and Ras modeled at the active site of RasGRP1 (orange). The helical hairpin of RasGRP1 is rotated ∼25° away from Ras relative to the helical hairpin of SOS in the inactive state. In this conformation, the helical hairpin of SOS occludes the Ras binding site.