View source for 8hlz


==F8-A22-E4 complex of MPXV in hexameric form==
<StructureSection load='8hlz' size='340' side='right'caption='[[8hlz]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8hlz]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Monkeypox_virus Monkeypox virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8HLZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8HLZ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.5&#8491;</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=8hlz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8hlz OCA], [https://pdbe.org/8hlz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8hlz RCSB], [https://www.ebi.ac.uk/pdbsum/8hlz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8hlz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q5IXP2_MONPV Q5IXP2_MONPV] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The ongoing global pandemic caused by a variant of the monkeypox (or mpox) virus (MPXV) has prompted widespread concern. The MPXV DNA polymerase holoenzyme, consisting of F8, A22, and E4, is vital for replicating the viral genome and represents a crucial target for the development of antiviral drugs. However, the assembly and working mechanism for the DNA polymerase holoenzyme of MPXV remains elusive. Here, we present the cryo-electron microscopy (cryo-EM) structure of the DNA polymerase holoenzyme at an overall resolution of 3.5 A. Unexpectedly, the holoenzyme is assembled as a dimer of heterotrimers, of which the extra interface between the thumb domain of F8 and A22 shows a clash between A22 and substrate DNA, suggesting an autoinhibition state. Addition of exogenous double-stranded DNA shifts the hexamer into trimer exposing DNA binding sites, potentially representing a more active state. Our findings provide crucial steps toward developing targeted antiviral therapies for MPXV and related viruses.

Structural basis for the assembly of the DNA polymerase holoenzyme from a monkeypox virus variant.,Li Y, Shen Y, Hu Z, Yan R Sci Adv. 2023 Apr 21;9(16):eadg2331. doi: 10.1126/sciadv.adg2331. Epub 2023 Apr , 19. PMID:37075110<ref>PMID:37075110</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8hlz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Monkeypox virus]]
[[Category: Hu ZW]]
[[Category: Li YN]]
[[Category: Shen YP]]
[[Category: Yan RH]]