4O4R

Murine Norovirus RdRp in complex with PPNDS

4O4R の概要

• エントリーDOI: 10.2210/pdb4o4r/pdb
• 分子名称: RNA-dependent-RNA-polymerase, 3-[(E)-{4-formyl-5-hydroxy-6-methyl-3-[(phosphonooxy)methyl]pyridin-2-yl}diazenyl]-7-nitronaphthalene-1,5-disulfonic acid, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: rna-dependent-rna-polymerase, rna binding, viral protein-replication inhibitor complex, viral protein/replication inhibitor
• 由来する生物種: Murine norovirus 1
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 179905.50

構造登録者

Croci, R.,Tarantino, D.,Milani, M.,Pezzullo, M.,Bolognesi, M.,Mastrangelo, E. (登録日: 2013-12-19, 公開日: 2014-11-05, 最終更新日: 2024-10-30)

主引用文献

Croci, R.,Tarantino, D.,Milani, M.,Pezzullo, M.,Rohayem, J.,Bolognesi, M.,Mastrangelo, E.
PPNDS inhibits murine Norovirus RNA-dependent RNA-polymerase mimicking two RNA stacking bases.
Febs Lett., 588:1720-1725, 2014

PubMed Abstract: Norovirus (NV) is a major cause of gastroenteritis worldwide. Antivirals against such important pathogens are on demand. Among the viral proteins that orchestrate viral replication, RNA-dependent-RNA-polymerase (RdRp) is a promising drug development target. From an in silico-docking search focused on the RdRp active site, we selected the compound PPNDS, which showed low micromolar IC50vs. murine NV-RdRp in vitro. We report the crystal structure of the murine NV-RdRp/PPNDS complex showing that two molecules of the inhibitor bind in antiparallel stacking interaction, properly oriented to block exit of the newly synthesized RNA. Such inhibitor-binding mode mimics two stacked nucleotide-bases of the RdRp/ssRNA complex.

PubMed: 24657439
DOI: 10.1016/j.febslet.2014.03.021

実験手法

X-RAY DIFFRACTION (2.4 Å)