Structural highlights
2a8s is a 2 chain structure with sequence from African clawed frog. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , |
| NonStd Res: | |
| Related: | 1u20, 2a8p, 2a8q, 2a8r, 2a8t |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[NUD16_XENLA] RNA-binding and decapping enzyme that catalyzes the cleavage of the cap structure of snoRNAs and mRNAs in a metal-dependent manner. Part of the U8 snoRNP complex that is required for the accumulation of mature 5.8S and 28S rRNA. Has diphosphatase activity and removes m7G and/or m227G caps from U8 snoRNA and leaves a 5'monophosphate on the RNA. Catalyzes also the cleavage of the cap structure on mRNAs. Does not hydrolyze cap analog structures like 7-methylguanosine nucleoside triphosphate (m7GpppG). Also hydrolysis m7G- and m227G U3-capped RNAs but with less efficiencies. Has broad substrate specificity with manganese or cobalt as cofactor and can act on various RNA species. Binds to the U8 snoRNA; metal is not required for RNA-binding. May play a role in the regulation of snoRNAs and mRNAs degradation. Acts also as a phosphatase; hydrolyzes the non-canonical purine nucleotides inosine diphosphate (IDP) and deoxyinosine diphosphate (dITP) as well as guanosine diphosphate (GDP), deoxyguanosine diphosphate (dGDP), xanthine diphosphate (XDP), inosine triphosphate (ITP) and deoxyinosine triphosphate (ITP) to their respective monophosphate derivatives and does not distinguish between the deoxy- and ribose forms. The order of activity with different substrates is IDP > dIDP >> GDP = dGDP > XDP = ITP = dITP. Binds strongly to GTP, ITP and XTP. Participates in the hydrolysis of dIDP/IDP and probably excludes non-canonical purines from RNA and DNA precursor pools, thus preventing their incorporation into RNA and DNA and avoiding chromosomal lesions.[1] [2] [3] [4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
X29, a 25 kDa Nudix hydrolase from Xenopus laevis that cleaves 5' caps from U8 snoRNA, crystallizes as a homodimeric apoenzyme. Manganese binds crystals of apo-X29 to form holo-X29 only in the presence of nucleot(s)ide. Structural changes in X29 on nucleo-t(s)ide-assisted Mn(+2) uptake account for the observed cooperativity of metal binding. Structures of X29 with GTP or m7GpppA show a different mode of ligand binding from that of other cap binding proteins and suggest a possible three- or four-metal Nudix reaction mechanism. The X29 dimer has no known RNA binding motif, but its striking surface dipolarity and unique structural features create a plausible RNA binding channel on the positive face of the protein. Because U8 snoRNP is essential for accumulation of mature 5.8S and 28S rRNA in vertebrate ribosome biogenesis, and cap structures are required for U8 stability in vivo, X29 could profoundly influence this fundamental cellular pathway.
Crystal structures of U8 snoRNA decapping nudix hydrolase, X29, and its metal and cap complexes.,Scarsdale JN, Peculis BA, Wright HT Structure. 2006 Feb;14(2):331-43. PMID:16472752[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ghosh T, Peterson B, Tomasevic N, Peculis BA. Xenopus U8 snoRNA binding protein is a conserved nuclear decapping enzyme. Mol Cell. 2004 Mar 26;13(6):817-28. PMID:15053875
- ↑ Tomasevic N, Peculis B. Identification of a U8 snoRNA-specific binding protein. J Biol Chem. 1999 Dec 10;274(50):35914-20. PMID:10585477
- ↑ Peculis BA, Reynolds K, Cleland M. Metal determines efficiency and substrate specificity of the nuclear NUDIX decapping proteins X29 and H29K (Nudt16). J Biol Chem. 2007 Aug 24;282(34):24792-805. Epub 2007 Jun 13. PMID:17567574 doi:http://dx.doi.org/M704179200
- ↑ Taylor MJ, Peculis BA. Evolutionary conservation supports ancient origin for Nudt16, a nuclear-localized, RNA-binding, RNA-decapping enzyme. Nucleic Acids Res. 2008 Oct;36(18):6021-34. doi: 10.1093/nar/gkn605. Epub 2008, Sep 27. PMID:18820299 doi:http://dx.doi.org/10.1093/nar/gkn605
- ↑ Scarsdale JN, Peculis BA, Wright HT. Crystal structures of U8 snoRNA decapping nudix hydrolase, X29, and its metal and cap complexes. Structure. 2006 Feb;14(2):331-43. PMID:16472752 doi:http://dx.doi.org/10.1016/j.str.2005.11.010
