a Crystal structure of PDE3ACAT-Xtl bound to DNMDP. Each monomer is colored dark and light blue. DNMDP is shown in space-filling for clarity with the carbon, oxygen, and nitrogen atoms colored green, red, and blue, respectively. The two loop regions replaced by linkers are indicated by dashed lines. b–d Catalytic sites from the PDE3ACAT-Xtl crystal structures. b PDE3ACAT-Xtl-AMP; c PDE3ACAT-Xtl-DNMDP; and d PDE3ACAT-Xtl-trequinsin are shown. The side chains are shown in a licorice format, with the carbon atoms colored white. The AMP, DNMDP, and trequinsin are shown in a similar format except the carbons that are colored green for visualization purposes. The phosphorus of AMP is shown in orange. The two metal ions and the coordinating water molecules are represented as gray and red spheres, respectively. Hydrogen bonds and metal–ligand interactions are shown as dashed yellow lines. e Analysis of the PDE3ACAT and SLFN12 interface by HDX-MS. D-uptake differences are mapped with green and blue onto the PDE3ACAT-Xtl crystal structure for 300 and 3000 s. BRD9500 is depicted with cyan spheres.