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| | <StructureSection load='4nz6' size='340' side='right'caption='[[4nz6]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='4nz6' size='340' side='right'caption='[[4nz6]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4nz6]] is a 2 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=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> | + | <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> |
| - | </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> | + | </td></tr><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> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4nz7|4nz7]]</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=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> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PUS1, PP8985 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <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>
| + | |
| - | <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://pdbe.org/4nz6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4nz6 RCSB], [http://www.ebi.ac.uk/pdbsum/4nz6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4nz6 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[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> | + | [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 == |
| - | [[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). | + | [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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| | *[[Guide-independent Pseudouridine synthase|Guide-independent Pseudouridine synthase]] | | *[[Guide-independent Pseudouridine synthase|Guide-independent Pseudouridine synthase]] |
| - | *[[Pseudouridine synthase|Pseudouridine synthase]] | + | *[[Pseudouridine synthase 3D structures|Pseudouridine synthase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Huet, T]] | + | [[Category: Huet T]] |
| - | [[Category: Thore, S]] | + | [[Category: Thore S]] |
| - | [[Category: Isomerase]]
| + | |
| - | [[Category: Mitochondrial]]
| + | |
| - | [[Category: Nuclear receptor coactivator]]
| + | |
| - | [[Category: Nucleus]]
| + | |
| - | [[Category: Pseudouridylation]]
| + | |
| - | [[Category: Steroid receptor rna activator]]
| + | |
| Structural highlights
Disease
PUS1_HUMAN Mitochondrial myopathy and sideroblastic anemia. The disease is caused by variants affecting the gene represented in this entry.
Function
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).[1] [2] [3] [4]
Publication Abstract from PubMed
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.
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[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Patton JR, Bykhovskaya Y, Mengesha E, Bertolotto C, Fischel-Ghodsian N. Mitochondrial myopathy and sideroblastic anemia (MLASA): missense mutation in the pseudouridine synthase 1 (PUS1) gene is associated with the loss of tRNA pseudouridylation. J Biol Chem. 2005 May 20;280(20):19823-8. doi: 10.1074/jbc.M500216200. Epub 2005 , Mar 16. PMID:15772074 doi:http://dx.doi.org/10.1074/jbc.M500216200
- ↑ Huet T, Miannay FA, Patton JR, Thore S. Steroid receptor RNA activator (SRA) modification by the human pseudouridine synthase 1 (hPus1p): RNA binding, activity, and atomic model. PLoS One. 2014 Apr 10;9(4):e94610. doi: 10.1371/journal.pone.0094610. eCollection, 2014. PMID:24722331 doi:http://dx.doi.org/10.1371/journal.pone.0094610
- ↑ Carlile TM, Martinez NM, Schaening C, Su A, Bell TA, Zinshteyn B, Gilbert WV. mRNA structure determines modification by pseudouridine synthase 1. Nat Chem Biol. 2019 Oct;15(10):966-974. doi: 10.1038/s41589-019-0353-z. Epub 2019, Sep 2. PMID:31477916 doi:http://dx.doi.org/10.1038/s41589-019-0353-z
- ↑ Martinez NM, Su A, Burns MC, Nussbacher JK, Schaening C, Sathe S, Yeo GW, Gilbert WV. Pseudouridine synthases modify human pre-mRNA co-transcriptionally and affect pre-mRNA processing. Mol Cell. 2022 Feb 3;82(3):645-659.e9. doi: 10.1016/j.molcel.2021.12.023. Epub, 2022 Jan 19. PMID:35051350 doi:http://dx.doi.org/10.1016/j.molcel.2021.12.023
- ↑ Huet T, Miannay FA, Patton JR, Thore S. Steroid receptor RNA activator (SRA) modification by the human pseudouridine synthase 1 (hPus1p): RNA binding, activity, and atomic model. PLoS One. 2014 Apr 10;9(4):e94610. doi: 10.1371/journal.pone.0094610. eCollection, 2014. PMID:24722331 doi:http://dx.doi.org/10.1371/journal.pone.0094610
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