Figure 3

Model of regulatory effect of Chk1 mutations. Using the same color scheme as in Figure 1: A. a postulated domain organization is shown. B. In its inactive state, the C-terminal domain interacts with the kinase domain to occlude the active site catalytic cleft. C. Phosphorylation opens the molecule to expose the catalytic cleft. D. Activating mutations such as E472D (red, in region 2) block the intramolecular interactions that occlude the catalytic cleft, activating Chk1's kinase activity. E. The E472D suppressor mutations in the kinase domain (Cyan) restore the intramolecular interaction to again occlude the active site. F. The molecule containing both E472D and a suppressor mutation can still be opened by S345 phosphorylation, restoring normal regulation in response to DNA damage.