3SFG

crystal structure of murine norovirus RNA dependent RNA polymerase in complex with 2thiouridine(2TU)

3SFG の概要

• エントリーDOI: 10.2210/pdb3sfg/pdb
• 関連するPDBエントリー: 3NAH 3NAI 3QID 3SFU
• 分子名称: RNA polymerase, 1-(beta-D-ribofuranosyl)-2-thioxo-2,3-dihydropyrimidin-4(1H)-one, SULFATE ION, ... (6 entities in total)
• 機能のキーワード: right hand conformation, polymerase, rna binding, transferase
• 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: 181404.45

構造登録者

Kim, K.H.,Alam, I. (登録日: 2011-06-13, 公開日: 2012-05-09, 最終更新日: 2024-10-30)

主引用文献

Alam, I.,Lee, J.H.,Cho, K.J.,Han, K.R.,Yang, J.M.,Chung, M.S.,Kim, K.H.
Crystal structures of murine norovirus-1 RNA-dependent RNA polymerase in complex with 2-thiouridine or ribavirin.
Virology, 426:143-151, 2012

PubMed Abstract: Murine norovirus-1 (MNV-1) shares many features with human norovirus (HuNoV) and both are classified within the norovirus genus of Caliciviridae family. MNV-1 is used as the surrogate for HuNoV research since it is the only form that can be grown in cell culture. HuNoV and MNV-1 RNA dependent RNA polymerase (RdRp) proteins with the sequence identity of 59% show essentially identical conformations. Here we report the first structural evidence of 2-thiouridine (2TU) or ribavirin binding to MNV-1 RdRp, based on the crystal structures determined at 2.2Å and 2.5Å resolutions, respectively. Cellular and biochemical studies revealed stronger inhibitory effect of 2TU on the replication of MNV-1 in RAW 264.7 cells, compared to that of ribavirin. Our complex structures highlight the key interactions involved in recognition of the nucleoside analogs which block the active site of the viral RNA polymerase.

PubMed: 22341781
DOI: 10.1016/j.virol.2012.01.016

実験手法

X-RAY DIFFRACTION (2.209 Å)