Structural and functional insights into the substrate specificity of the pseudouridine monophosphate phosphatase HDHD1A.

ABSTRACT: Pseudouridine (Ψ) is one of the most abundant RNA modifications. Following RNA degradation, Ψ nucleotides are dephosphorylated and catabolized into uracil and ribose 5'-phosphate via a two-step enzymatic reaction catalyzed by enzymes present in many bacteria and eukaryotes, but not in mammals. Malfunction of Ψ catabolism has adverse physiological effects in plants. In humans, the enzyme HDHD1A dephosphorylates pseudouridine 5'-monophosphate (ΨMP), and the resulting Ψ is excreted in the urine. In this study, we determined the crystal structures of human HDHD1A (hHDHD1A) complexed with Ψ. The structure of hHDHD1A consists of a catalytic domain with a Rossmann α/β-fold and a cap domain, with a magnesium ion at the junction of the two domains. Ψ is bound to the active site in an orientation wh

SUBMITTER: Seo S 

PROVIDER: S-EPMC12212127 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature