Fig. 2. Structure of α2KD bound to BAY-3827.

(A) Cocrystal structure of α2KD (shown as ribbons) with BAY-3827 (shown as yellow sticks). The activation loop (AL) segment is colored magenta. (B) Stereo-image of the 2Fo-Fc omit map of BAY-3827 shown at 1σ. (C) Magnified view of the BAY-3827 binding site with interactions indicated as gray dash lines. The side chains of Asp¹⁵⁷ and Phe¹⁵⁸ of the DFG motif are shown as sticks with Phe¹⁵⁸ in an “FG down” conformation. A water molecule (W) is shown as a red sphere. A disulfide bond (Cys¹⁰⁶-Cys¹⁷⁴) is shown as sticks. (D) Stereo image of the Fo-Fc polder map (Phenix) of the indicated disulfide bond between Cys¹⁰⁶ from αD and Cys¹⁷⁴ from activation loop (AL). (E) Surface view of α2KD bound to BAY-3827 with superimposed compound C (light cyan, PDB:3AQV) and SBI-0206965 green, PDB:6BX6) inhibitors shown with sticks (29, 33, 80). (F) Zoomed-in view of the DFG motif superimposed with compound C (light cyan, PDB: 3AQV) and SBI-0206965 (green, PDB:6BX6), displaying the backbone (as ribbons) of α2KD bound to BAY-3827 showing key regulatory spine residues.