6dx2: Difference between revisions
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==Crystal structure of the viral OTU domain protease from Dera Ghazi Khan virus== | |||
<StructureSection load='6dx2' size='340' side='right'caption='[[6dx2]], [[Resolution|resolution]] 1.61Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6dx2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Dera_Ghazi_Khan_orthonairovirus Dera Ghazi Khan orthonairovirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DX2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DX2 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]] 1.614Å</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=6dx2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dx2 OCA], [https://pdbe.org/6dx2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dx2 RCSB], [https://www.ebi.ac.uk/pdbsum/6dx2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dx2 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A191KW82_9VIRU A0A191KW82_9VIRU] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Post-translational modification of host and viral proteins by ubiquitin (Ub) and Ub-like proteins, such as interferon stimulated gene product 15 (ISG15), plays a key role in response to infection. Viruses have been increasingly identified that contain proteases possessing deubiquitinase (DUB) and/or deISGylase functions. This includes viruses in the Nairoviridae family that encode a viral homologue of the ovarian tumor protease (vOTU). vOTU activity was recently demonstrated to be critical for replication of the often-fatal Crimean-Congo hemorrhagic fever virus, with DUB activity suppressing the type I interferon responses and deISGylase activity broadly removing ISG15 conjugated proteins. There are currently about 40 known nairoviruses classified into fourteen species. Recent genomic characterization has revealed a high degree of diversity, with vOTUs showing less than 25% amino acids identities within the family. Previous investigations have been limited to only a few closely related nairoviruses, leaving it unclear what impact this diversity has on vOTU function. To probe the effects of vOTU diversity on enzyme activity and specificity, we assessed representative vOTUs spanning the Nairoviridae family towards Ub and ISG15 fluorogenic substrates. This revealed great variation in enzymatic activity and specific substrate preferences. A subset of the vOTUs were further assayed against eight biologically relevant di-Ub substrates, uncovering both common trends and distinct preferences of poly-Ub linkages by vOTUs. Four novel X-ray crystal structures were obtained that provide a biochemical rationale for vOTU substrate preferences and elucidate structural features that distinguish the vOTUs, including a motif in the Hughes orthonairovirus species that has not been previously observed in OTU domains. Additionally, structure-informed mutagenesis provided the first direct evidence of a second site involved in di-Ub binding for vOTUs. These results provide new insight into nairovirus evolution and pathogenesis, and further enhances the development of tools for therapeutic purposes. | |||
Probing the impact of nairovirus genomic diversity on viral ovarian tumor domain protease (vOTU) structure and deubiquitinase activity.,Dzimianski JV, Beldon BS, Daczkowski CM, Goodwin OY, Scholte FEM, Bergeron E, Pegan SD PLoS Pathog. 2019 Jan 10;15(1):e1007515. doi: 10.1371/journal.ppat.1007515., eCollection 2019 Jan. PMID:30629698<ref>PMID:30629698</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Beldon | <div class="pdbe-citations 6dx2" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: Dzimianski | ==See Also== | ||
[[Category: | *[[RNA polymerase 3D structures|RNA polymerase 3D structures]] | ||
[[Category: | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Dera Ghazi Khan orthonairovirus]] | |||
[[Category: Large Structures]] | |||
[[Category: Beldon BS]] | |||
[[Category: Daczkowski CM]] | |||
[[Category: Dzimianski JV]] | |||
[[Category: Goodwin OY]] | |||
[[Category: Pegan SD]] | |||