2HCS

Crystal structure of RNA dependant RNA polymerase domain of West Nile virus

2HCS の概要

• エントリーDOI: 10.2210/pdb2hcs/pdb
• 関連するPDBエントリー: 2HCN
• 分子名称: RNA-directed RNA polymerase (NS5), ZINC ION (3 entities in total)
• 機能のキーワード: west-nile virus rna polymerase, structural genomics, marseilles structural genomics program @ afmb, msgp, vizier, viral enzymes involved in replication, transferase
• 由来する生物種: Kunjin virus
• 細胞内の位置: Capsid protein C: Virion (Potential). Peptide pr: Secreted (By similarity). Small envelope protein M: Virion membrane; Multi-pass membrane protein (By similarity). Envelope protein E: Virion membrane; Multi- pass membrane protein (By similarity). Non-structural protein 1: Secreted. Non-structural protein 2A: Host endoplasmic reticulum membrane; Multi-pass membrane protein (Potential). Serine protease subunit NS2B: Host endoplasmic reticulum membrane; Multi-pass membrane protein (Potential). Serine protease NS3: Host endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side (By similarity). Non-structural protein 4A: Host endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity). Non-structural protein 4B: Host endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity). RNA-directed RNA polymerase NS5: Host endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side (By similarity): P14335
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 68462.47

構造登録者

Egloff, M.P.,Malet, H.,Marseilles Structural Genomics Program @ AFMB (MSGP) (登録日: 2006-06-18, 公開日: 2007-02-06, 最終更新日: 2024-02-14)

主引用文献

Malet, H.,Egloff, M.P.,Selisko, B.,Butcher, R.E.,Wright, P.J.,Roberts, M.,Gruez, A.,Sulzenbacher, G.,Vonrhein, C.,Bricogne, G.,Mackenzie, J.M.,Khromykh, A.A.,Davidson, A.D.,Canard, B.
Crystal structure of the RNA polymerase domain of the West Nile virus non-structural protein 5
J.Biol.Chem., 282:10678-10689, 2007

PubMed Abstract: Viruses of the family Flaviviridae are important human and animal pathogens. Among them, the Flaviviruses dengue (DENV) and West Nile (WNV) cause regular outbreaks with fatal outcomes. The RNA-dependent RNA polymerase (RdRp) activity of the non-structural protein 5 (NS5) is a key activity for viral RNA replication. In this study, crystal structures of enzymatically active and inactive WNV RdRp domains were determined at 3.0- and 2.35-A resolution, respectively. The determined structures were shown to be mostly similar to the RdRps of the Flaviviridae members hepatitis C and bovine viral diarrhea virus, although with unique elements characteristic for the WNV RdRp. Using a reverse genetic system, residues involved in putative interactions between the RNA-cap methyltransferase (MTase) and the RdRp domain of Flavivirus NS5 were identified. This allowed us to propose a model for the structure of the full-length WNV NS5 by in silico docking of the WNV MTase domain (modeled from our previously determined structure of the DENV MTase domain) onto the RdRp domain. The Flavivirus RdRp domain structure determined here should facilitate both the design of anti-Flavivirus drugs and structure-function studies of the Flavivirus replication complex in which the multifunctional NS5 protein plays a central role.

PubMed: 17287213
DOI: 10.1074/jbc.M607273200

実験手法

X-RAY DIFFRACTION (2.5 Å)