Figure 7.

Crystal structures of CHK2 kinase in complex with inhibitors: (A) compound 30, (B) compound 19, (C) compound 44 and (D) compound 47. The protein is shown in ribbon format, including cylinder representation for residues within 4 Å of the inhibitor (or the water molecule bridging the inhibitor and the hinge). An omit map showing Fo-Fc density is shown in green and contoured at 3.0σ. While strong electron density was present in each dataset for the 2-(4-oxyphenyl)-1H-benzo[d]imidazole-5-carboxamide scaffold, the weak density for the phenolic substituent of compound 19 (Panel B) suggested two alternate conformations for this moiety. The benzyl and chlorobenzyl groups of compound 44 and 47 (Panels C and D) were completely disordered, and have not been modelled. Electron density corresponding to the water molecule bridging the benzimidazole and the hinge region was observed in all four structures, but, after refinement, was omitted from the model for compound 19 (Panel B). Proposed H-bonds are indicated by black dotted lines. A summary of the data collection and refinement statistics is presented in Supplementary data (Table S5).