10YZ

Crystal structure of mouse DXO in complex with pGGGUU RNA and two magnesium ions

Summary for 10YZ

• Entry DOI: 10.2210/pdb10yz/pdb
• Descriptor: Decapping and exoribonuclease protein, RNA (5'-R(GP*GP*GP*UP*U)-3'), MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: dxo, rna, decapping, exoribonuclease, hydrolase, hydrolase-rna complex, hydrolase/rna
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 2
• Total formula weight: 46987.89

Authors

Doamekpor, S.K.,Tong, L. (deposition date: 2026-02-12, release date: 2026-06-10)

Primary citation

Ullah, N.,Doamekpor, S.K.,Tong, L.
Crystal structure of mouse DXO in complex with the UDP-N-acetylglucosamine cap and molecular mechanism for the decapping reactions.
Nucleic Acids Res., 54:-, 2026

PubMed 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.

PubMed: 42200294
DOI: 10.1093/nar/gkag521

Experimental method

X-RAY DIFFRACTION (1.6 Å)