9PNL

Influenza PA-N Endonuclease E23K mutant with compound 4 ((6M)-3-hydroxy-4-oxo-6-(2-phenoxyphenyl)-1,4-dihydropyridine-2-carboxylic acid)

これはPDB形式変換不可エントリーです。

9PNL の概要

• エントリーDOI: 10.2210/pdb9pnl/pdb
• 関連するPDBエントリー: 9PMP 9PMR 9PN2 9PN3
• 分子名称: Polymerase acidic protein, MANGANESE (II) ION, (6M)-3-hydroxy-4-oxo-6-(2-phenoxyphenyl)-1,4-dihydropyridine-2-carboxylic acid, ... (4 entities in total)
• 機能のキーワード: metal binding protein, endonuclease, influenza endonuclease, lyase
• 由来する生物種: Influenza A virus (A/California/04/2009(H1N1))
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 22767.67

構造登録者

Kohlbrand, A.J. (登録日: 2025-07-21, 公開日: 2026-01-21)

主引用文献

Kohlbrand, A.J.,Stokes, R.W.,Sankaran, B.,Cohen, S.M.
Substituent size versus metal binding of inhibitors with variants of influenza endonuclease.
J.Inorg.Biochem., 277:113210-113210, 2025

PubMed Abstract: The influenza virus causes a significant burden of illness each year. Although vaccination is the most effective method to prevent seasonal influenza infection, viral escape mechanisms make vaccine composition difficult to predict. Antivirals are crucial for decreasing rates of morbidity and mortality from influenza viral infection. The newest anti-influenza drugs target the RNA-dependent RNA polymerase acidic N-terminal (PA) endonuclease, a critical component of influenza viral replication machinery. This study examines the structure of inhibitors of PA that utilize a hydroxypyridinone-based metal-binding pharmacophore (MBP). Specifically, this report explores how the size of substituent groups impacts the binding conformation and affinity of a series of compounds against both wild-type (WT) and resistance mutant strains, I38T and E23K. Co-crystal structures revealed that the distance between compounds and enzyme residue 38 was conserved to maintain strong interactions, resulting in deviations from ideal coordination geometries at the active site metal centers. This suggests the interactions with residue 38 with each compound is important and can impact inhibitor potency as a consequence of distortions in the metal binding geometry of the compounds.

PubMed: 41512630
DOI: 10.1016/j.jinorgbio.2025.113210

実験手法

X-RAY DIFFRACTION (2.21 Å)