4nz6

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==Steroid receptor RNA Activator (SRA) modification by the human Pseudouridine Synthase 1 (hPus1p): RNA binding, activity, and atomic model==
==Steroid receptor RNA Activator (SRA) modification by the human Pseudouridine Synthase 1 (hPus1p): RNA binding, activity, and atomic model==
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<StructureSection load='4nz6' size='340' side='right' caption='[[4nz6]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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<StructureSection load='4nz6' size='340' side='right'caption='[[4nz6]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4nz6]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NZ6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NZ6 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4nz6]] is a 2 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=4NZ6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NZ6 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DGL:D-GLUTAMIC+ACID'>DGL</scene>, <scene name='pdbligand=DLY:D-LYSINE'>DLY</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4nz7|4nz7]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DGL:D-GLUTAMIC+ACID'>DGL</scene>, <scene name='pdbligand=DLY:D-LYSINE'>DLY</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/tRNA_pseudouridine(38-40)_synthase tRNA pseudouridine(38-40) synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.4.99.12 5.4.99.12] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4nz6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nz6 OCA], [https://pdbe.org/4nz6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nz6 RCSB], [https://www.ebi.ac.uk/pdbsum/4nz6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nz6 ProSAT]</span></td></tr>
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<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=4nz6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nz6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4nz6 RCSB], [http://www.ebi.ac.uk/pdbsum/4nz6 PDBsum]</span></td></tr>
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</table>
</table>
== Disease ==
== Disease ==
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[[http://www.uniprot.org/uniprot/TRUA_HUMAN TRUA_HUMAN]] Mitochondrial myopathy and sideroblastic anemia. Myopathy with lactic acidosis and sideroblastic anemia 1 (MLASA1) [MIM:[http://omim.org/entry/600462 600462]]: A rare oxidative phosphorylation disorder specific to skeletal muscle and bone marrow. Affected individuals manifest progressive muscle weakness, exercise intolerance, lactic acidosis, sideroblastic anemia and delayed growth. Note=The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:15108122</ref>
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[https://www.uniprot.org/uniprot/PUS1_HUMAN PUS1_HUMAN] Mitochondrial myopathy and sideroblastic anemia. The disease is caused by variants affecting the gene represented in this entry.
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/TRUA_HUMAN TRUA_HUMAN]] Converts specific uridines to PSI in a number of tRNA substrates. Acts on positions 27/28 in the anticodon stem and also positions 34 and 36 in the anticodon of an intron containing tRNA. Involved in regulation of nuclear receptor activity possibly through pseudouridylation of SRA1 RNA (By similarity).
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[https://www.uniprot.org/uniprot/PUS1_HUMAN PUS1_HUMAN] Pseudouridylate synthase that catalyzes pseudouridylation of tRNAs and mRNAs (PubMed:15772074, PubMed:24722331). Acts on positions 27/28 in the anticodon stem and also positions 34 and 36 in the anticodon of an intron containing tRNA (PubMed:24722331). Also catalyzes pseudouridylation of mRNAs: mediates pseudouridylation of mRNAs with the consensus sequence 5'-UGUAG-3' (PubMed:31477916, PubMed:35051350). Acts as a regulator of pre-mRNA splicing by mediating pseudouridylation of pre-mRNAs at locations associated with alternatively spliced regions (PubMed:35051350). Pseudouridylation of pre-mRNAs near splice sites directly regulates mRNA splicing and mRNA 3'-end processing (PubMed:35051350). Involved in regulation of nuclear receptor activity through pseudouridylation of SRA1 mRNA (PubMed:24722331).<ref>PMID:15772074</ref> <ref>PMID:24722331</ref> <ref>PMID:31477916</ref> <ref>PMID:35051350</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The most abundant of the modified nucleosides, and once considered as the "fifth" nucleotide in RNA, is pseudouridine, which results from the action of pseudouridine synthases. Recently, the mammalian pseudouridine synthase 1 (hPus1p) has been reported to modulate class I and class II nuclear receptor responses through its ability to modify the Steroid receptor RNA Activator (SRA). These findings highlight a new level of regulation in nuclear receptor (NR)-mediated transcriptional responses. We have characterised the RNA association and activity of the human Pus1p enzyme with its unusual SRA substrate. We validate that the minimal RNA fragment within SRA, named H7, is necessary for both the association and modification by hPus1p. Furthermore, we have determined the crystal structure of the catalytic domain of hPus1p at 2.0 A resolution, alone and in a complex with several molecules present during crystallisation. This model shows an extended C-terminal helix specifically found in the eukaryotic protein, which may prevent the enzyme from forming a homodimer, both in the crystal lattice and in solution. Our biochemical and structural data help to understand the hPus1p active site architecture, and detail its particular requirements with regard to one of its nuclear substrates, the non-coding RNA SRA.
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Steroid receptor RNA activator (SRA) modification by the human pseudouridine synthase 1 (hPus1p): RNA binding, activity, and atomic model.,Huet T, Miannay FA, Patton JR, Thore S PLoS One. 2014 Apr 10;9(4):e94610. doi: 10.1371/journal.pone.0094610. eCollection, 2014. PMID:24722331<ref>PMID:24722331</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==See Also==
==See Also==
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*[[TRNA pseudouridine synthase|TRNA pseudouridine synthase]]
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*[[Guide-independent Pseudouridine synthase|Guide-independent Pseudouridine synthase]]
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*[[Pseudouridine synthase 3D structures|Pseudouridine synthase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Huet, T]]
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[[Category: Homo sapiens]]
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[[Category: Thore, S]]
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[[Category: Large Structures]]
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[[Category: Isomerase]]
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[[Category: Huet T]]
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[[Category: Mitochondrial]]
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[[Category: Thore S]]
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[[Category: Nuclear receptor coactivator]]
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[[Category: Nucleus]]
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[[Category: Pseudouridylation]]
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[[Category: Steroid receptor rna activator]]
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Current revision

Steroid receptor RNA Activator (SRA) modification by the human Pseudouridine Synthase 1 (hPus1p): RNA binding, activity, and atomic model

PDB ID 4nz6

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