Structural Basis for the Selective Inhibition of Cdc2-Like Kinases by CX-4945
Figure 5
Comparison of the CX-4945 binding mode. (a) Electrostatic surface representation of the CX-4945 binding pocket of CLK1. The bound CX-4945 is shown in yellow. The residues surrounding the binding pocket are labeled. The asterisk indicates the main chain of the corresponded residue. The blue and red colors represent positive and negative charges, respectively. (b) Electrostatic surface representation of the CX-4945 binding pocket of CLK2. The bound CX-4945 is shown in yellow. The residues surrounding the binding pocket are labeled. The asterisk indicates the main chain of the corresponded residue. (c) Electrostatic surface representation of the CX-4945 binding pocket of CLK3. The bound CX-4945 is shown in yellow. The residues surrounding the binding pocket are labeled. The asterisk indicates the main chain of the corresponded residue. (d) Superposition of the CLK2/CX-4945 and CK2/CX-4945 (PDB code; 3PEI) complexes. The CLK2/CX-4945 complex is colored in light purple. In the CK2/CX-4945 complex, α-helices and β-sheets are colored in salmon, and loops are colored in pink. The detailed view of bound CX-4945 is shown in a square box (yellow for CK2 and light purple for CLK2). The positions of the bound CX-4945 in CLK2 and CK2 are almost identical. (e) The CK2/CX-4945 complex in coordination with a CX-4945 molecule (yellow) and water molecules in the active site. The residues of both α-helices and β-sheets are shown in salmon, and one loop is colored in pink. The four small red spheres represent water molecules. Hydrogen bonds between CK2 and CX-4945 are shown as black dashed lines.