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{{STRUCTURE_4its|  PDB=4its  |  SCENE=  }}
==Crystal structure of the catalytic domain of human Pus1 with MES in the active site==
===Crystal structure of the catalytic domain of human Pus1 with MES in the active site===
<StructureSection load='4its' size='340' side='right' caption='[[4its]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
{{ABSTRACT_PUBMED_23707380}}
== Structural highlights ==
 
<table><tr><td colspan='2'>[[4its]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ITS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ITS FirstGlance]. <br>
==Disease==
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</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]], [[4j37|4j37]]</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 Homo sapiens])</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=4its FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4its OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4its RCSB], [http://www.ebi.ac.uk/pdbsum/4its PDBsum]</span></td></tr>
</table>
== 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>   
[[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>   
== 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).
<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.


==Function==
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>
[[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).  


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[4its]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ITS OCA].
</div>


==Reference==
==See Also==
<ref group="xtra">PMID:023707380</ref><references group="xtra"/><references/>
*[[TRNA pseudouridine synthase|TRNA pseudouridine synthase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Czudnochowski, N.]]
[[Category: Czudnochowski, N]]
[[Category: Finer-Moore, J S.]]
[[Category: Finer-Moore, J S]]
[[Category: Stroud, R M.]]
[[Category: Stroud, R M]]
[[Category: Beta sheet]]
[[Category: Beta sheet]]
[[Category: Isomerase]]
[[Category: Isomerase]]

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