1r6a
From Proteopedia
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'''Structure of the dengue virus 2'O methyltransferase in complex with s-adenosyl homocysteine and ribavirin 5' triphosphate''' | '''Structure of the dengue virus 2'O methyltransferase in complex with s-adenosyl homocysteine and ribavirin 5' triphosphate''' | ||
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[[Category: Romette, J L.]] | [[Category: Romette, J L.]] | ||
[[Category: 2'o methyltransferase]] | [[Category: 2'o methyltransferase]] | ||
| - | [[Category: | + | [[Category: Dengue virus]] |
| - | [[Category: | + | [[Category: Ribavirin 5'-triphosphate]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 07:08:09 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 04:08, 3 May 2008
Structure of the dengue virus 2'O methyltransferase in complex with s-adenosyl homocysteine and ribavirin 5' triphosphate
Overview
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.
About this Structure
1R6A is a Single protein structure of sequence from Dengue virus 2. Full crystallographic information is available from OCA.
Reference
A structural basis for the inhibition of the NS5 dengue virus mRNA 2'-O-methyltransferase domain by ribavirin 5'-triphosphate., Benarroch D, Egloff MP, Mulard L, Guerreiro C, Romette JL, Canard B, J Biol Chem. 2004 Aug 20;279(34):35638-43. Epub 2004 May 19. PMID:15152003 Page seeded by OCA on Sat May 3 07:08:09 2008
