Structural Basis for the Selective Inhibition of Cdc2-Like Kinases by CX-4945
Figure 4
CX-4945 binding sites of CLKs. (a) The 2Fo-Fc electron densities of the CX-4945 molecules bound in CLK1, CLK2, and CLK3 are shown at the 1.0 σ contoured level. (b) Active site residues in coordination with CX-4945 (yellow) in the structure of the CLK1/CX-4945 complex. The small red spheres (W1 and W2) indicate water molecules. Dashed black lines represent interactions between ligands and residues. Nitrogen, oxygen, and chlorine are colored in blue, red, and black, respectively. The N-lobe and C-lobe are colored in cyan and blue, respectively. All residues are shown in light cyan. (c) Binding pocket of CLK2/CX-4945 in coordination with a CX-4945 molecule (yellow). The small red sphere (W1) indicates a water molecule. The N-lobe and C-lobe are colored in light green and purple, respectively. All residues are shown in light green. (d) CLK3/CX-4945 in coordination with a CX-4945 molecule (yellow) and a water molecule (W1) in the active site. The N-lobe and C-lobe are colored in pink and light purple, respectively. All residues are shown in pink.