Fig. 3: Structural studies reveal conserved functional residues in DNPH1.
From: Mechanism of substrate hydrolysis by the human nucleotide pool sanitiser DNPH1
a, b Focused views of hmdUMP bound to the active site of DNPH1E104Q chain B (yellow) supplemented by interactions from chain A (light blue). Green dotted lines highlight key hydrogen bond interactions. a Intra- and inter-molecular interactions stabilise ligand phosphate and hydroxymethyl moieties. b Rotated view of (a) highlighting active site arrangements and substrate positioning. E104Q is inappropriately oriented for nucleophilic attack (magenta dotted line) at the anomeric carbon. H56 interacts with the base carbonyl oxygen O2. c Superposition of DNPH1E104Q chain B (yellow) bound to hmdUMP with MilBE103A (PDB 4OHB; green) bound to hmCMP. RMSD between 77 Cα atom pairs = 0.902 Å. The relative positions of ligands are remarkably similar. d Close-up view of hmCMP (grey sticks) bound to the active site of MilBE103A (green), for comparison with DNPH1E104Q binding to hmdUMP, as shown in b Fig. 2b E62 stabilises the substrate via hydrogen bonds (green dotted lines) with nitrogen moieties on the base. Sidechains of active site/interacting residues are shown as sticks; ligand/sidechain oxygen, nitrogen and phosphorus atoms are coloured red, blue and orange respectively. Bond distances are given in Å to 1 decimal place.
