Mode of binding of CMP6 to JAK2 kinase domain. (A) Interactions between CMP6 and JAK2 kinase domain. The side chains of residues that interact with the inhibitor are shown, as are main-chain atoms and water molecules participating in hydrogen bonds. The N-terminal lobe is colored in gray, the hinge region in yellow-green, the activation loop in red, and the catalytic loop in blue. Selected hydrogen bonds are shown as black lines. (B) View of the catalytic cleft of JAK2 bound to CMP6 presented in a ball-and-stick representation and covered with the final 2Fo-Fc electron density map contoured at 1σ. The coloring of the backbone representation is the same as in panel A. (C) Structural formula of CMP6 presented in a ball-and-stick representation.