View source for 6wre


==Crystal structure of mouse DXO in complex with 5'-OH RNA substrate mimic and calcium ion==
<StructureSection load='6wre' size='340' side='right'caption='[[6wre]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6wre]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WRE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WRE 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]] 2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=U37:URIDINE+5-MONOTHIOPHOSPHATE'>U37</scene>, <scene name='pdbligand=U3P:3-URIDINEMONOPHOSPHATE'>U3P</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=6wre FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wre OCA], [https://pdbe.org/6wre PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wre RCSB], [https://www.ebi.ac.uk/pdbsum/6wre PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wre ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DXO_MOUSE DXO_MOUSE] Ribonuclease that specifically degrades pre-mRNAs with a defective 5' end cap and is part of a pre-mRNA capping quality control. Has decapping, pyrophosphohydrolase and 5'-3' exonuclease activities. Has decapping activity toward incomplete 5' end cap mRNAs such as unmethylated 5' end-capped RNA to release GpppN and 5' end monophosphate RNA. The 5' end monophosphate RNA is then degraded by the 5'-3' exoribonuclease activity, enabling this enzyme to decap and degrade incompletely capped mRNAs. Also possesses RNA 5'-pyrophosphohydrolase activity by hydrolyzing the 5' end triphosphate to release pyrophosphates.<ref>PMID:23523372</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Modifications at the 5'-end of RNAs play a pivotal role in determining their fate. In eukaryotes, the DXO/Rai1 family of enzymes removes numerous 5'-end RNA modifications, thereby regulating RNA turnover. Mouse DXO catalyzes the elimination of incomplete 5'-end caps (including pyrophosphate) and the non-canonical NAD+ cap on mRNAs, and possesses distributive 5'-3' exoribonuclease activity toward 5'-monophosphate (5'-PO4) RNA. Here, we demonstrate that DXO also catalyzes the hydrolysis of RNAs bearing a 5'-hydroxyl group (5'-OH RNA). The crystal structure of DXO in complex with a 5'-OH RNA substrate mimic at 2.0 A resolution provides elegant insight into the molecular mechanism of this activity. More importantly, the structure predicts that DXO first removes a dinucleotide from 5'-OH RNA. Our nuclease assays confirm this prediction and demonstrate that this 5'-hydroxyl dinucleotide hydrolase (HDH) activity for DXO is higher than the subsequent 5'-3' exoribonuclease activity for selected substrates. Fission yeast Rai1 also has HDH activity although it does not have 5'-3' exonuclease activity, and the Rat1-Rai1 complex can completely degrade 5'-OH RNA. An Arabidopsis DXO1 variant is active toward 5'-OH RNA but prefers 5'-PO4 RNA. Collectively, these studies demonstrate the diverse activities of DXO/Rai1 and expands the collection of RNA substrates that can undergo 5'-3' mediated decay.

A novel 5'-hydroxyl dinucleotide hydrolase activity for the DXO/Rai1 family of enzymes.,Doamekpor SK, Gozdek A, Kwasnik A, Kufel J, Tong L Nucleic Acids Res. 2020 Jan 10;48(1):349-358. doi: 10.1093/nar/gkz1107. PMID:31777937<ref>PMID:31777937</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6wre" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Doamekpor SK]]
[[Category: Tong L]]