8K8U

F8-A22-E4 complex of MPXV in complex with DNA and dCTP

8K8U の概要

• エントリーDOI: 10.2210/pdb8k8u/pdb
• EMDBエントリー: 36962
• 分子名称: DNA polymerase F8, Uracil-DNA glycosylase E4, DNA polymerase processivity factor component A20, ... (8 entities in total)
• 機能のキーワード: recombination, replication, viral protein-dna complex, viral protein/dna
• 由来する生物種: Monkeypox virus; 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 200498.40

構造登録者

Shen, Y.P.,Li, Y.N.,Yan, R.H. (登録日: 2023-07-31, 公開日: 2024-06-05, 最終更新日: 2024-06-19)

主引用文献

Shen, Y.,Li, Y.,Yan, R.
Structural basis for the inhibition mechanism of the DNA polymerase holoenzyme from mpox virus.
Structure, 32:654-661.e3, 2024

PubMed Abstract: 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 Å 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.

PubMed: 38579705
DOI: 10.1016/j.str.2024.03.004

実験手法

ELECTRON MICROSCOPY (3.05 Å)