Document Type
Article
Publication Date
5-20-2026
Abstract
Noncanonical metabolite 5' caps have recently been identified on RNAs, and the DXO/Rai1 family of enzymes can remove these caps in eukaryotes. While the binding modes of NAD, FAD and dephospho-CoA (dpCoA) caps in the active site of mouse DXO have been determined, how DXO recognizes the UDP-glucose (UDP-Glc) and UDP-N-acetylglucosamine (UDP-GlcNAc) caps is not known. In addition, the molecular mechanism by which DXO catalyzes the decapping reactions is still poorly understood, especially the location of the water/hydroxide that attacks the scissile phosphate to initiate the decapping. Here we report the crystal structure of mouse DXO in complex with UDP-GlcNAc at 1.8 Å resolution. The binding mode of the compound explains why DXO removes the entire cap from RNA. We have also determined the structures of mouse DXO in complex with purine oligonucleotides, pA5 and pGGGUU. Most importantly, we have produced a model of DXO in a catalytically competent complex with substrates, revealing that a water/hydroxide coordinated to the first metal ion is the nucleophile that attacks the scissile phosphate. The conformation of the scissile phosphate is similar to an alternate conformer of the 5' phosphate in pA5, which provides experimental support for the modeled substrate complex.
Recommended Citation
Ullah, Najeeb; Doamekpor, Selom K.; and Tong, Liang, "Crystal Structure of Mouse DXO in Complex With the UDP-N-Acetylglucosamine Cap and Molecular Mechanism for the Decapping Reactions" (2026). Department of Biochemistry and Molecular Biology Faculty Papers. Paper 300.
https://jdc.jefferson.edu/bmpfp/300
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
42200294
Language
English
Comments
This article is the author’s final published version in Nucleic Acids Research, Volume 54, Issue 10, 2026.
The published version is available at https://doi.org/10.1093/nar/gkag521. Copyright © The Author(s) 2026.