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==HSV-1 DNA polymerase-processivity factor complex in exonuclease state==
<StructureSection load='8oja' size='340' side='right'caption='[[8oja]], [[Resolution|resolution]] 1.87&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8oja]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_alphaherpesvirus_1_strain_KOS Human alphaherpesvirus 1 strain KOS] 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=8OJA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8OJA 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]] 1.87&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AS:2-DEOXY-ADENOSINE+-5-THIO-MONOPHOSPHATE'>AS</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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=8oja FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8oja OCA], [https://pdbe.org/8oja PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8oja RCSB], [https://www.ebi.ac.uk/pdbsum/8oja PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8oja ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DPOL_HHV11 DPOL_HHV11] Replicates viral genomic DNA. The replication complex is composed of six viral proteins: the DNA polymerase, processivity factor, primase, primase-associated factor, helicase, and ssDNA-binding protein. Additionally, the polymerase contains an intrinsic ribonuclease H (RNase H) activity that specifically degrades RNA/DNA heteroduplexes or duplex DNA substrates in the 5' to 3' direction. Therefore, it can catalyze the excision of the RNA primers that initiate the synthesis of Okazaki fragments at a replication fork during viral DNA replication.<ref>PMID:2553735</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Herpes simplex virus 1 (HSV-1), a double-stranded DNA virus, replicates using seven essential proteins encoded by its genome. Among these, the UL30 DNA polymerase, complexed with the UL42 processivity factor, orchestrates leading and lagging strand replication of the 152 kb viral genome. UL30 polymerase is a prime target for antiviral therapy, and resistance to current drugs can arise in immunocompromised individuals. Using electron cryo-microscopy (cryo-EM), we unveil the dynamic changes of the UL30/UL42 complex with DNA in three distinct states. First, a pre-translocation state with an open fingers domain ready for nucleotide incorporation. Second, a halted elongation state where the fingers close, trapping dATP in the dNTP pocket. Third, a DNA-editing state involving significant conformational changes to allow DNA realignment for exonuclease activity. Additionally, the flexible UL30 C-terminal domain interacts with UL42, forming an extended positively charged surface binding to DNA, thereby enhancing processive synthesis. These findings highlight substantial structural shifts in the polymerase and its DNA interactions during replication, offering insights for future antiviral drug development.

Dynamics of the Herpes simplex virus DNA polymerase holoenzyme during DNA synthesis and proof-reading revealed by Cryo-EM.,Gustavsson E, Grunewald K, Elias P, Hallberg BM Nucleic Acids Res. 2024 May 29:gkae374. doi: 10.1093/nar/gkae374. PMID:38806233<ref>PMID:38806233</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8oja" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human alphaherpesvirus 1 strain KOS]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Elias P]]
[[Category: Grunewald K]]
[[Category: Gustavsson E]]
[[Category: Hallberg BM]]