Steve Ealick's Research Group

Pseudouridine Monophosphate Glycosidase

PDB files:

4GIJ ΨMP glycosidase

4GIK R5P adduct

4GIL ΨMP covalent adduct

4GIM K166A/ΨMP complex


Pseudouridine, Ψ, the most abundant modification in RNA, is synthesized in situ using Ψ synthase. For degradation, Ψ is first converted to Ψ 5´-monophosphate (ΨMP) by Ψ kinase and then ΨMP is degraded by ΨMP glycosidase to uracil and ribose 5-phosphate. ΨMP glycosidase is the first example of a mechanistically-characterized enzyme that cleaves a C-C glycosidic bond. Our four structures provide snapshots along the reaction coordinate.

The glycosidase shows an αβα fold with an eleven-stranded central β sheet.


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ΨMP glycosidase is a homotrimer, with the trimer interface formed primarily by helices α5 and α8 from one protomer and helices α9 and α10 from the adjacent protomer. 

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Each protomer has an active site is in a cleft that includes well-ordered water molecules around the manganese coordination sphere.

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Huang S, Mahanta N, Begley TP, and Ealick SE. Pseudouridine Monophosphate Glycosidase: A New Glycosidase Mechanism. Biochemistry 51:9245-9255 (2012). PubMed

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