1r6a
From Proteopedia
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| - | [[Image:1r6a.jpg|left|200px]] | + | [[Image:1r6a.jpg|left|200px]] |
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| - | '''Structure of the dengue virus 2'O methyltransferase in complex with s-adenosyl homocysteine and ribavirin 5' triphosphate''' | + | {{Structure |
| + | |PDB= 1r6a |SIZE=350|CAPTION= <scene name='initialview01'>1r6a</scene>, resolution 2.6Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene> and <scene name='pdbligand=RVP:RIBAVIRIN MONOPHOSPHATE'>RVP</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] | ||
| + | |GENE= NS5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11069 Dengue virus type 3]) | ||
| + | }} | ||
| + | |||
| + | '''Structure of the dengue virus 2'O methyltransferase in complex with s-adenosyl homocysteine and ribavirin 5' triphosphate''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1R6A is a [ | + | 1R6A is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Dengue_virus_type_3 Dengue virus type 3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R6A OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/15152003 15152003] |
[[Category: Dengue virus type 3]] | [[Category: Dengue virus type 3]] | ||
[[Category: RNA-directed RNA polymerase]] | [[Category: RNA-directed RNA polymerase]] | ||
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[[Category: ribavirin 5'-triphosphate]] | [[Category: ribavirin 5'-triphosphate]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:47:32 2008'' |
Revision as of 11:47, 20 March 2008
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| , resolution 2.6Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , and | ||||||
| Gene: | NS5 (Dengue virus type 3) | ||||||
| Activity: | RNA-directed RNA polymerase, with EC number 2.7.7.48 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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 type 3. 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
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