View source for 4j37


==Crystal structure of the catalytic domain of human Pus1==
<StructureSection load='4j37' size='340' side='right'caption='[[4j37]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
== Structural highlights ==
<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.75&#8491;</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='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>
</table>
== Disease ==
[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 ==
[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;">
== 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<ref>PMID:23707380</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4j37" style="background-color:#fffaf0;"></div>

==See Also==
*[[Guide-independent Pseudouridine synthase|Guide-independent Pseudouridine synthase]]
*[[Pseudouridine synthase 3D structures|Pseudouridine synthase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Czudnochowski N]]
[[Category: Finer-Moore JS]]
[[Category: Stroud RM]]