9NEE

The flexible portion of Cryo-EM structure of Herpesvirus Helicase-Primase complex with Pritelivir

これはPDB形式変換不可エントリーです。

9NEE の概要

• エントリーDOI: 10.2210/pdb9nee/pdb
• EMDBエントリー: 49306
• 分子名称: DNA primase, DNA replication helicase, Pritelivir (3 entities in total)
• 機能のキーワード: inhibitor, herpesvirus, helicase, primase, pritelivir, replication, transferase-inhibitor complex, transferase/inhibitor
• 由来する生物種: Herpesviridae; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 210075.15

構造登録者

Yao, Q.,Yu, X. (登録日: 2025-02-19, 公開日: 2025-08-13, 最終更新日: 2026-02-25)

主引用文献

Yao, Q.,Mercier, A.,Nayak, A.,May, L.,Ho, P.Y.,Lewis-Ballester, A.,Nair, V.,Sapre, A.,Aeschbacher, T.,Mukherjee, J.,Richards, C.,Mateo, R.,Cho, A.,Lansdon, E.,Yu, X.
Structural and mechanistic insights into herpesvirus helicase-primase and its therapeutic inhibitors.
Nat Microbiol, 10:3191-3201, 2025

PubMed Abstract: The herpes simplex virus (HSV) helicase-primase (HP) complex is a promising anti-herpes therapeutic target. However, progress in developing highly effective small-molecule HP inhibitors (HPIs) for the treatment of genital herpes has been hindered by the lack of structural information on the HP complex and the incomplete understanding of the mechanism of action of HPIs. Here we present the cryogenic electron microscopy structure of the HSV-1 HP apo-complex (3.8 Å), along with structures bound to pritelivir (3.2 Å) and amenamevir (3.2 Å)-two clinically active, chemically distinct HPIs. The potency of both inhibitors against HSV variants bearing mutations within the HPI binding pocket supports the high-resolution mapping of key molecular interactions while revealing residues that govern their antiviral spectrum against alphaherpesviruses. Our results provide important insight into the unique architecture of the HP complex and the mechanism of inhibition of HPIs, paving the way for the development of next-generation antivirals to treat herpesvirus infections.

PubMed: 41188384
DOI: 10.1038/s41564-025-02168-4

実験手法

ELECTRON MICROSCOPY (3.2 Å)