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| | <StructureSection load='4j37' size='340' side='right'caption='[[4j37]], [[Resolution|resolution]] 1.75Å' scene=''> | | <StructureSection load='4j37' size='340' side='right'caption='[[4j37]], [[Resolution|resolution]] 1.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4j37]] is a 1 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=4J37 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4J37 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4j37]] is a 1 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=4J37 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4J37 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4iqm|4iqm]], [[4its|4its]]</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=4j37 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j37 OCA], [https://pdbe.org/4j37 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4j37 RCSB], [https://www.ebi.ac.uk/pdbsum/4j37 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4j37 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=4j37 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j37 OCA], [http://pdbe.org/4j37 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4j37 RCSB], [http://www.ebi.ac.uk/pdbsum/4j37 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4j37 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: Czudnochowski, N]] | + | [[Category: Czudnochowski N]] |
| - | [[Category: Finer-Moore, J S]] | + | [[Category: Finer-Moore JS]] |
| - | [[Category: Stroud, R M]] | + | [[Category: Stroud RM]] |
| - | [[Category: Beta sheet]]
| + | |
| - | [[Category: Isomerase]]
| + | |
| - | [[Category: Pre-trna]]
| + | |
| - | [[Category: Pseudouridine synthase]]
| + | |
| - | [[Category: Rna binding protein]]
| + | |
| - | [[Category: Steroid receptor rna activator]]
| + | |
| - | [[Category: Trna]]
| + | |
| - | [[Category: U2 snrna]]
| + | |
| 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
Human pseudouridine (Psi) synthase Pus1 (hPus1) modifies specific uridine residues in several non-coding RNAs: tRNA, U2 spliceosomal RNA, and steroid receptor activator RNA. We report three structures of the catalytic core domain of hPus1 from two crystal forms, at 1.8A resolution. The structures are the first of a mammalian Psi synthase from the set of five Psi-synthase families common to all kingdoms of life. Pus1 adopts a fold similar to bacterial Psi synthases, with a central antiparallel beta-sheet flanked by helices and loops. A flexible hinge at the base of the sheet allows the enzyme to open and close around an electropositive active-site cleft. In one crystal form, a molecule of Mes [2-(N-morpholino)ethane sulfonic acid] mimics the target uridine of an RNA substrate. A positively charged electrostatic surface extends from the active site towards the N-terminus of the catalytic domain, suggesting an extensive binding site specific for target RNAs. Two alpha-helices C-terminal to the core domain, but unique to hPus1, extend along the back and top of the central beta-sheet and form the walls of the RNA binding surface. Docking of tRNA to hPus1 in a productive orientation requires only minor conformational changes to enzyme and tRNA. The docked tRNA is bound by the electropositive surface of the protein employing a completely different binding mode than that seen for the tRNA complex of the Escherichia coli homologue TruA.
In Human Pseudouridine Synthase 1 (hPus1), a C-Terminal Helical Insert Blocks tRNA from Binding in the Same Orientation as in the Pus1 Bacterial Homologue TruA, Consistent with Their Different Target Selectivities.,Czudnochowski N, Wang AL, Finer-Moore J, Stroud RM J Mol Biol. 2013 May 23. pii: S0022-2836(13)00328-8. doi:, 10.1016/j.jmb.2013.05.014. PMID:23707380[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
- ↑ Czudnochowski N, Wang AL, Finer-Moore J, Stroud RM. In Human Pseudouridine Synthase 1 (hPus1), a C-Terminal Helical Insert Blocks tRNA from Binding in the Same Orientation as in the Pus1 Bacterial Homologue TruA, Consistent with Their Different Target Selectivities. J Mol Biol. 2013 May 23. pii: S0022-2836(13)00328-8. doi:, 10.1016/j.jmb.2013.05.014. PMID:23707380 doi:10.1016/j.jmb.2013.05.014
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