1R6A

Structure of the dengue virus 2'O methyltransferase in complex with s-adenosyl homocysteine and ribavirin 5' triphosphate

1R6A の概要

• エントリーDOI: 10.2210/pdb1r6a/pdb
• 関連するPDBエントリー: 1L9K
• 分子名称: Genome polyprotein, SULFATE ION, S-ADENOSYL-L-HOMOCYSTEINE, ... (5 entities in total)
• 機能のキーワード: ribavirin 5'-triphosphate, dengue virus, 2'o methyltransferase, transferase
• 由来する生物種: Dengue virus 2 Puerto Rico/PR159-S1/1969
• 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-alpha: Host endoplasmic reticulum membrane; Multi-pass membrane protein (Potential). Non-structural protein 2A: Host endoplasmic reticulum membrane; Multi-pass membrane protein (Potential). Serine protease subunit NS2B: Host endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side (By similarity). 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): P12823
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34526.71

構造登録者

Benarroch, D.,Egloff, M.P.,Mulard, L.,Romette, J.L.,Canard, B. (登録日: 2003-10-15, 公開日: 2004-09-21, 最終更新日: 2024-02-14)

主引用文献

Benarroch, D.,Egloff, M.P.,Mulard, L.,Guerreiro, C.,Romette, J.L.,Canard, B.
A structural basis for the inhibition of the NS5 dengue virus mRNA 2'-O-methyltransferase domain by ribavirin 5'-triphosphate.
J.Biol.Chem., 279:35638-35643, 2004

PubMed Abstract: Ribavirin is one of the few nucleoside analogues currently used in the clinic to treat RNA virus infections, but its mechanism of action remains poorly understood at the molecular level. Here, we show that ribavirin 5'-triphosphate inhibits the activity of the dengue virus 2'-O-methyltransferase NS5 domain (NS5MTase(DV)). Along with several other guanosine 5'-triphosphate analogues such as acyclovir, 5-ethynyl-1-beta-d-ribofuranosylimidazole-4-carboxamide (EICAR), and a series of ribose-modified ribavirin analogues, ribavirin 5'-triphosphate competes with GTP to bind to NS5MTase(DV). A structural view of the binding of ribavirin 5'-triphosphate to this enzyme was obtained by determining the crystal structure of a ternary complex consisting of NS5MTase(DV), ribavirin 5'-triphosphate, and S-adenosyl-l-homocysteine at a resolution of 2.6 A. These detailed atomic interactions provide the first structural insights into the inhibition of a viral enzyme by ribavirin 5'-triphosphate, as well as the basis for rational drug design of antiviral agents with improved specificity against the emerging flaviviruses.

PubMed: 15152003
DOI: 10.1074/jbc.M400460200

実験手法

X-RAY DIFFRACTION (2.6 Å)