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| | ==Crystal structure of tRNA-dihydrouridine(20) synthase dsRBD domain== | | ==Crystal structure of tRNA-dihydrouridine(20) synthase dsRBD domain== |
| - | <StructureSection load='4wft' size='340' side='right' caption='[[4wft]], [[Resolution|resolution]] 1.70Å' scene=''> | + | <StructureSection load='4wft' size='340' side='right'caption='[[4wft]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4wft]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WFT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WFT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4wft]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WFT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WFT FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DUS2, DUS2L ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4wft FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wft OCA], [https://pdbe.org/4wft PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wft RCSB], [https://www.ebi.ac.uk/pdbsum/4wft PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wft ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4wft FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wft OCA], [http://pdbe.org/4wft PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4wft RCSB], [http://www.ebi.ac.uk/pdbsum/4wft PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4wft ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DUS2L_HUMAN DUS2L_HUMAN]] Dihydrouridine synthase. Catalyzes the synthesis of dihydrouridine, a modified base found in the D-loop of most tRNAs. Negatively regulates the activation of EIF2AK2/PKR.<ref>PMID:15994936</ref> <ref>PMID:18096616</ref> | + | [https://www.uniprot.org/uniprot/DUS2L_HUMAN DUS2L_HUMAN] Dihydrouridine synthase. Catalyzes the synthesis of dihydrouridine, a modified base found in the D-loop of most tRNAs. Negatively regulates the activation of EIF2AK2/PKR.<ref>PMID:15994936</ref> <ref>PMID:18096616</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Bregeon, D]] | + | [[Category: Large Structures]] |
| - | [[Category: Fontecave, M]] | + | [[Category: Bou Nader C]] |
| - | [[Category: Golinelli-Pimpaneau, B]] | + | [[Category: Bregeon D]] |
| - | [[Category: Guimaraes, B G]] | + | [[Category: Fontecave M]] |
| - | [[Category: Hamdane, D]] | + | [[Category: Golinelli-Pimpaneau B]] |
| - | [[Category: Kamah, A]] | + | [[Category: Guimaraes BG]] |
| - | [[Category: Nader, C Bou]]
| + | [[Category: Hamdane D]] |
| - | [[Category: Pecqueur, L]] | + | [[Category: Kamah A]] |
| - | [[Category: Rna binding protein]]
| + | [[Category: Pecqueur L]] |
| - | [[Category: Rna binding protein oxidoreductase]]
| + | |
| Structural highlights
Function
DUS2L_HUMAN Dihydrouridine synthase. Catalyzes the synthesis of dihydrouridine, a modified base found in the D-loop of most tRNAs. Negatively regulates the activation of EIF2AK2/PKR.[1] [2]
Publication Abstract from PubMed
In tRNA, dihydrouridine is a conserved modified base generated by the post-transcriptional reduction of uridine. Formation of dihydrouridine 20, located in the D-loop, is catalyzed by dihydrouridine synthase 2 (Dus2). Human Dus2 (HsDus2) expression is upregulated in lung cancers, offering a growth advantage throughout its ability to interact with components of the translation apparatus and inhibit apoptosis. Here, we report the crystal structure of the individual domains of HsDus2 and their functional characterization. HsDus2 is organized into three major modules. The N-terminal catalytic domain contains the flavin cofactor involved in the reduction of uridine. The second module is the conserved alpha-helical domain known as the tRNA binding domain in HsDus2 homologues. It is connected via a flexible linker to an unusual extended version of a dsRNA binding domain (dsRBD). Enzymatic assays and yeast complementation showed that the catalytic domain binds selectively NADPH but cannot reduce uridine in the absence of the dsRBD. While in Dus enzymes from bacteria, plants and fungi, tRNA binding is essentially achieved by the alpha-helical domain, we showed that in HsDus2 this function is carried out by the dsRBD. This is the first reported case of a tRNA-modifying enzyme carrying a dsRBD used to bind tRNAs.
An extended dsRBD is required for post-transcriptional modification in human tRNAs.,Bou-Nader C, Pecqueur L, Bregeon D, Kamah A, Guerineau V, Golinelli-Pimpaneau B, Guimaraes BG, Fontecave M, Hamdane D Nucleic Acids Res. 2015 Oct 1. pii: gkv989. PMID:26429968[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kato T, Daigo Y, Hayama S, Ishikawa N, Yamabuki T, Ito T, Miyamoto M, Kondo S, Nakamura Y. A novel human tRNA-dihydrouridine synthase involved in pulmonary carcinogenesis. Cancer Res. 2005 Jul 1;65(13):5638-46. PMID:15994936 doi:http://dx.doi.org/65/13/5638
- ↑ Mittelstadt M, Frump A, Khuu T, Fowlkes V, Handy I, Patel CV, Patel RC. Interaction of human tRNA-dihydrouridine synthase-2 with interferon-induced protein kinase PKR. Nucleic Acids Res. 2008 Feb;36(3):998-1008. Epub 2007 Dec 20. PMID:18096616 doi:http://dx.doi.org/10.1093/nar/gkm1129
- ↑ Bou-Nader C, Pecqueur L, Bregeon D, Kamah A, Guerineau V, Golinelli-Pimpaneau B, Guimaraes BG, Fontecave M, Hamdane D. An extended dsRBD is required for post-transcriptional modification in human tRNAs. Nucleic Acids Res. 2015 Oct 1. pii: gkv989. PMID:26429968 doi:http://dx.doi.org/10.1093/nar/gkv989
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