8k8s: Difference between revisions
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The | ==F8-A22-E4 complex of MPXV in complex with DNA and Ara-CTP== | ||
<StructureSection load='8k8s' size='340' side='right'caption='[[8k8s]], [[Resolution|resolution]] 3.06Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8k8s]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/DNA_molecule DNA molecule] and [https://en.wikipedia.org/wiki/Monkeypox_virus Monkeypox virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8K8S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8K8S 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]] 3.06Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HF4:4-amino-1-{5-O-[(S)-hydroxy{[(R)-hydroxy(phosphonooxy)phosphoryl]oxy}phosphoryl]-beta-D-arabinofuranosyl}pyrimidin-2(1H)-one'>HF4</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=8k8s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8k8s OCA], [https://pdbe.org/8k8s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8k8s RCSB], [https://www.ebi.ac.uk/pdbsum/8k8s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8k8s ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q5IXP2_MONPV Q5IXP2_MONPV] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
There are three key components at the core of the mpox virus (MPXV) DNA polymerase holoenzyme: DNA polymerase F8, processivity factors A22, and the Uracil-DNA glycosylase E4. The holoenzyme is recognized as a vital antiviral target because MPXV replicates in the cytoplasm of host cells. Nucleotide analogs such as cidofovir and cytarabine (Ara-C) have shown potential in curbing MPXV replication and they also display promise against other poxviruses. However, the mechanism behind their inhibitory effects remains unclear. Here, we present the cryo-EM structure of the DNA polymerase holoenzyme F8/A22/E4 bound with its competitive inhibitor Ara-C-derived cytarabine triphosphate (Ara-CTP) at an overall resolution of 3.0 A and reveal its inhibition mechanism. Ara-CTP functions as a direct chain terminator in proximity to the deoxycytidine triphosphate (dCTP)-binding site. The extra hydrogen bond formed with Asn665 makes it more potent in binding than dCTP. Asn665 is conserved among eukaryotic B-family polymerases. | |||
Structural basis for the inhibition mechanism of the DNA polymerase holoenzyme from mpox virus.,Shen Y, Li Y, Yan R Structure. 2024 Mar 26:S0969-2126(24)00086-8. doi: 10.1016/j.str.2024.03.004. PMID:38579705<ref>PMID:38579705</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8k8s" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: DNA molecule]] | |||
[[Category: Large Structures]] | |||
[[Category: Monkeypox virus]] | |||
[[Category: Li YN]] | |||
[[Category: Shen YP]] | |||
[[Category: Yan RH]] | |||