Fig. 5: Crystal structures of Form D with ligands of interest.
From: WRN structural flexibility showcased through fragment-based lead discovery of inhibitors
A Overlay of fragment 1-bound WRN (blue) and AMP-PNP-bound WRN (white) structures is aligned on the D1 domains and shows the approximate 180° rotation of the D2 domain. B WRN helicase loop consisting of residues Val570-Ser578. This loop closes into and abrogates the binding pocket when fragment 1 is bound. C Structure PDB 8PFO (teal) in Form B superposed with fragment 1-bound WRN (dark blue) in Form D. D Interactions between fragment 1 and WRN residues highlighted in yellow dashes. E Overlay of fragment 2 (orange) with fragment 1 (blue) shows similar ligand binding modes. F Fragment 2 interactions with WRN residues highlighted by yellow dashes.
