View source for 7jms


==Structure of the Hazara virus OTU bound to ubiquitin==
<StructureSection load='7jms' size='340' side='right'caption='[[7jms]], [[Resolution|resolution]] 2.78&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7jms]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Hazara_orthonairovirus Hazara orthonairovirus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7JMS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JMS 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]] 2.78&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AYE:PROP-2-EN-1-AMINE'>AYE</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=7jms FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jms OCA], [https://pdbe.org/7jms PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jms RCSB], [https://www.ebi.ac.uk/pdbsum/7jms PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jms ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A6XA53_9VIRU A6XA53_9VIRU] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Nairoviruses are arthropod-borne viruses with a nearly global geographical distribution. Several are known causative agents of human disease, including Crimean-Congo hemorrhagic fever virus (CCHFV), which has a case fatality rate that can exceed 30%. Nairoviruses encode an ovarian tumour domain protease (OTU) that can suppress the innate immune response by reversing post-translational modifications by ubiquitin (Ub) and/or interferon-stimulated gene product 15 (ISG15). As a result, the OTU has been identified as a potential target for the development of CCHFV therapeutics. Despite sharing the same general fold, nairoviral OTUs show structural and enzymatic diversity. The CCHFV OTU, for example, possesses activity towards both Ub and ISG15, while the Hazara virus (HAZV) OTU interacts exclusively with Ub. Virology studies focused on the OTU have mostly been restricted to CCHFV, which requires BSL-4 containment facilities. Although HAZV has been proposed as a BSL-2 alternative, differences in the engagement of substrates by CCHFV and HAZV OTUs may present complicating factors when trying to model one using the other. To understand the molecular underpinnings of the differences in activity, a 2.78 A resolution crystal structure of HAZV OTU bound to Ub was solved. Using structure-guided site-directed mutagenesis, HAZV OTUs were engineered with altered or eliminated deubiquitinase activity, including one with an exclusive activity for ISG15. Additionally, analysis of the structure yielded insights into the difference in inhibition observed between CCHFV and HAZV OTUs with a Ub-based inhibitor. These new insights present opportunities to utilize HAZV as a model system to better understand the role of the OTU in the context of infection.

Flipping the substrate preference of Hazara virus ovarian tumour domain protease through structure-based mutagenesis.,Dzimianski JV, Mace SL, Williams IL, Freitas BT, Pegan SD Acta Crystallogr D Struct Biol. 2020 Nov 1;76(Pt 11):1114-1123. doi:, 10.1107/S2059798320012875. Epub 2020 Oct 16. PMID:33135682<ref>PMID:33135682</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7jms" style="background-color:#fffaf0;"></div>

==See Also==
*[[3D structures of ubiquitin|3D structures of ubiquitin]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Hazara orthonairovirus]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Dzimianski JV]]
[[Category: Pegan SD]]