Binding of AFN941 to Jak3 active site. (A) Structure of AFN941 juxtaposed with that of staurosporine. (B) Stereoview of the catalytic cleft of Jak3 bound to AFN941. The protein backbone trace is shown in the region of the active site with residues Leu828, Phe833, Val836, Ala853, Lys855, Met902, Glu903, Cys909, Arg953, Leu956, Ala966, and Asp967 depicted in stick representation. Staurosporine analog AFN941 is shown in stick representation with carbon atoms colored yellow. Carbonyl oxygens of residues Arg953 and Glu903 are shown in red, and water 2053 is depicted as a red sphere. Residue numbers are indicated. Hydrogen bonds to backbone atoms and water are indicated and their distances are noted. (C) Stereoview of the catalytic cleft of Jak3 bound to the staurosporine analog AFN941. The experimental F_obs - F_calc electron density omit map contoured at 2.5σ in blue is shown for the ligand AFN941. The glycine-rich loop is shown in purple and the activation loop in red. Residues proximal to the active site and divergent between Jak3 and Jak2 are shown in orange stick format and are labeled by Jak3 residue type, Jak3 residue number, and Jak2 residue type. These residues are Ser828Gln, Leu838Met, Cys909Ser, Arg916Lys, Ala966Gly, and Gln988Glu. (D) Location of point mutation Leu910Ser noted in human SCID patients.⁴  Leu910 is colored purple and indicated by the arrow.