View source for 8dzk


==Dbr1 in complex with 5-mer cleavage product==
<StructureSection load='8dzk' size='340' side='right'caption='[[8dzk]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8dzk]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Entamoeba_histolytica Entamoeba histolytica] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DZK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DZK 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]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=G46:GUANOSINE-5-MONOTHIOPHOSPHATE'>G46</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=8dzk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dzk OCA], [https://pdbe.org/8dzk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dzk RCSB], [https://www.ebi.ac.uk/pdbsum/8dzk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dzk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/C4M1P9_ENTH1 C4M1P9_ENTH1] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The RNA lariat debranching enzyme is the sole enzyme responsible for hydrolyzing the 2'-5' phosphodiester bond in RNA lariats produced by the spliceosome. Here, we test the ability of Dbr1 to hydrolyze branched RNAs (bRNAs) that contain a 2'-5'-phosphorothioate linkage, a modification commonly used to resist degradation. We attempted to cocrystallize a phosphorothioate-branched RNA (PS-bRNA) with wild-type Entamoeba histolytica Dbr1 (EhDbr1) but observed in-crystal hydrolysis of the phosphorothioate bond. The crystal structure revealed EhDbr1 in a product-bound state, with the hydrolyzed 2'-5' fragment of the PS-bRNA mimicking the binding mode of the native bRNA substrate. These findings suggest that product inhibition may contribute to the kinetic mechanism of Dbr1. We show that Dbr1 enzymes cleave phosphorothioate linkages at rates approximately 10,000-fold more slowly than native phosphate linkages. This new product-bound crystal structure offers atomic details, which can aid inhibitor design. Dbr1 inhibitors could be therapeutic or investigative compounds for human diseases such as human immunodeficiency virus (HIV), amyotrophic lateral sclerosis (ALS), cancer, and viral encephalitis.

Crystal Structure of the RNA Lariat Debranching Enzyme Dbr1 with Hydrolyzed Phosphorothioate RNA Product.,Clark NE, Katolik A, Welch A, Schorl C, Holloway SP, Schuermann JP, Hart PJ, Taylor AB, Damha MJ, Fairbrother WG Biochemistry. 2022 Dec 20;61(24):2933-2939. doi: 10.1021/acs.biochem.2c00590. , Epub 2022 Dec 9. PMID:36484984<ref>PMID:36484984</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8dzk" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Entamoeba histolytica]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Clark NE]]
[[Category: Taylor AB]]