3LKZ

Structural and functional analyses of a conserved hydrophobic pocket of flavivirus methyltransferase

3LKZ の概要

• エントリーDOI: 10.2210/pdb3lkz/pdb
• 関連するPDBエントリー: 2OY0
• 分子名称: Non-structural protein 5, SINEFUNGIN, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: west nile virus, flavivirus, methyltransferase, inhibitor, pocket, nucleotide-binding, rna replication, viral protein
• 由来する生物種: West Nile virus (WNV)
• 細胞内の位置: Envelope protein E: Virion membrane; Multi- pass membrane protein: Q9Q6P4
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 74432.59

構造登録者

Liu, L.H.,Li, H.M. (登録日: 2010-01-28, 公開日: 2010-08-04, 最終更新日: 2023-09-06)

主引用文献

Dong, H.,Liu, L.,Zou, G.,Zhao, Y.,Li, Z.,Lim, S.P.,Shi, P.Y.,Li, H.
Structural and functional analyses of a conserved hydrophobic pocket of flavivirus methyltransferase.
J.Biol.Chem., 285:32586-32595, 2010

PubMed Abstract: The flavivirus methyltransferase (MTase) sequentially methylates the N7 and 2'-O positions of the viral RNA cap (GpppA-RNA → m(7)GpppA-RNA → m(7)GpppAm-RNA), using S-adenosyl-l-methionine (AdoMet) as a methyl donor. We report here that sinefungin (SIN), an AdoMet analog, inhibits several flaviviruses through suppression of viral MTase. The crystal structure of West Nile virus MTase in complex with SIN inhibitor at 2.0-Å resolution revealed a flavivirus-conserved hydrophobic pocket located next to the AdoMet-binding site. The pocket is functionally critical in the viral replication and cap methylations. In addition, the N7 methylation efficiency was found to correlate with the viral replication ability. Thus, SIN analogs with modifications that interact with the hydrophobic pocket are potential specific inhibitors of flavivirus MTase.

PubMed: 20685660
DOI: 10.1074/jbc.M110.129197

実験手法

X-RAY DIFFRACTION (2 Å)