8k8s | pdb_00008k8s

F8-A22-E4 complex of MPXV in complex with DNA and Ara-CTP

spinqualitylabelsall models 8k8s, resolution 3.06Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8k8s is a 5 chain structure with sequence from DNA molecule and Monkeypox virus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.06Å Ligands: HF4, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q5IXP2_MONPV 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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