Fig. 2: Structure of DCLK1-KD:XMD8-85.
From: Structural basis for small molecule targeting of Doublecortin Like Kinase 1 with DCLK1-IN-1
a The structure of two molecules of DCLK1-KD:XMD8-85 within the asymmetric unit in a “head-to-tail” arrangement. b The structure of two molecules of DCLK1-KD:AMPPN (PDB 5JZJ) within the asymmetric unit in a “head-to-tail” and “face-to-face” arrangement. c Overlay of DCLK1-KD:XMD8-85 with DCLK1-KD:NVP-TAE684 showing the conservation of the canonical salt-bridge between Glu436 and Lys419 and differences in the αC helix conformation. d Top view of the overlay of DCLK1-KD:XMD8-85 with DCLK1-KD:NVP-TAE684. XMD8-85, rings B and A sits deeper into the back pocket within the ATP binding site. e Close up of the interaction of DCLK1-KD with XMD-8-85. f Water mediated network formed by the diazepine ring B with the invariant Lys419 and Glu436. g Surface representation of DCLK1-KD:XMD8-85 to highlight the cavity around the water-mediated network described in f. h The DCLK1-KD:XMD8-85 crystal structure identified two cavities, cavity 1 and 2) near the back pocket within the ATP binding site that could be exploited to achieve selectivity towards DCLK1. The h-bond and van der Waals interaction are shown in black and red dashed lines, respectively. The missing residues in DCLK1-KD:XMD8-85 are shown in pink dashed lines. Water molecules are shown as blue spheres. AMPN, magenta; XMD8-85, yellow; NVP-TAE684, cyan.
