Fig. 6: Mechanism of cleavage of hmdUMP by DNPH1.
From: Mechanism of substrate hydrolysis by the human nucleotide pool sanitiser DNPH1
H56 stabilises the hmU leaving group, which is protonated by D80 upon glycosidic bond cleavage (top left). Nucleophilic attack by E104 then promotes cleavage resulting in the formation of a covalent glycosyl-enzyme intermediate (right). E55 promotes water activation and cleavage of the glycosyl-ester bond. H56 is repositioned to facilitate this second step by enforcing an interaction between E104 and the ribose hydroxyl (bottom centre). Departure of the cleaved dRP allows enzyme reset and fresh substrate binding (bottom left).
