Fig. 4: Structure of DCLK1-KD:DCLK1-IN-1.
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:DCLK1-IN-1 within the asymmetric unit in a “head-to-tail” arrangement. b Close up of the interaction of DCLK1-KD with DCLK1-IN-1. c Overlay of DCLK1-Cter:FMF-03-055-1 with DCLK1-KD:DCLK1-IN-1 to highlight the opening of the ATP binding site and surface representation of DCLK1-KD:DCLK1-IN-1 showing the site occupied by a PEG molecule. The region near the glycine loop undergoes an upward shift (arrows indicated) by 5 Å (distance measured at the Cα atom of Ile396 located at the start of the glycine loop and Ala402 located at the end of the loop) to accommodate the bulky trifluoroethyl group. d Surface representation of DCLK1-KD:XMD8-85, DCLK1-Cter:FMF-03-055-1 and DCLK1-KD:DCLK1-IN-1 and ligand interaction diagrams generated using Schrödinger Maestro. The missing residues in DCLK1-KD: DCLK1-IN-1 are shown in grey dashed lines. The h-bond and van der Waals interaction are shown in black and red dashed lines, respectively. DCLK1-IN-1, purple; FMF-03-055-1, magenta. See also Supplementary Figs. 6 and 7.
