7I2E

Group deposition for crystallographic fragment screening of the NS5 RNA-dependent RNA polymerase from Dengue virus serotype 2 -- Crystal structure of the NS5 RNA-dependent RNA polymerase from Dengue virus serotype 2 in complex with Z740611958 (DNV2_NS5A-x0264)

これはPDB形式変換不可エントリーです。

7I2E の概要

• エントリーDOI: 10.2210/pdb7i2e/pdb
• Group deposition: Group deposition for crystallographic fragment screening of the NS5 RNA-dependent RNA polymerase from Dengue virus serotype 2 (G_1002341)
• 分子名称: NS5 RNA-dependent RNA polymerase, ZINC ION, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (9 entities in total)
• 機能のキーワード: diamond light source, i04-1, readdi, dengue virus, crystallographic fragment screening, pandda, xchemexplorer, cluster4x, viral protein
• 由来する生物種: dengue virus type 2
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 74930.18

構造登録者

Aschenbrenner, J.C.,Saini, M.,Chopra, A.,Marples, P.G.,Balcomb, B.H.,Lithgo, R.M.,Fearon, D.,von Delft, F.,Ruiz, F.X.,Arnold, E. (登録日: 2025-03-06, 公開日: 2025-04-02, 最終更新日: 2026-06-24)

主引用文献

Saini, M.,Aschenbrenner, J.C.,Ruiz, F.X.,Chopra, A.,Chandran, A.V.,Marples, P.G.,Balcomb, B.H.,Fearon, D.,von Delft, F.,Arnold, E.
Crystallographic Fragment Screening of the Dengue Virus Polymerase Reveals Multiple Binding Sites for the Development of Non-nucleoside Antiflavivirals.
J.Med.Chem., 68:18356-18369, 2025

PubMed Abstract: Dengue viruses (DENVs) infect approximately 400 million people each year, and currently, there are no effective therapeutics available. To explore potential starting points for antiviral drug development, we conducted a large-scale crystallographic fragment screen targeting the RNA-dependent RNA polymerase (RdRp) domain of the nonstructural protein 5 (NS5) from DENV serotype 2. Our screening, which involved 1108 fragments, identified 60 hit compounds across various known binding sites, including the active site, N pocket, and RNA tunnel. Additionally, we discovered a novel binding site and a fragment-binding hot spot in thumb site II. These structural findings open amenable avenues for developing non-nucleoside inhibitors and offer valuable insights for future structure-based drug design aimed at DENV and other flaviviral RdRps.

PubMed: 40892049
DOI: 10.1021/acs.jmedchem.5c01014

実験手法

X-RAY DIFFRACTION (1.72 Å)