1r6a: Difference between revisions
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New page: left|200px<br /><applet load="1r6a" size="450" color="white" frame="true" align="right" spinBox="true" caption="1r6a, resolution 2.6Å" /> '''Structure of the deng... |
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[[Image:1r6a.jpg|left|200px]]<br /><applet load="1r6a" size=" | [[Image:1r6a.jpg|left|200px]]<br /><applet load="1r6a" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1r6a, resolution 2.6Å" /> | caption="1r6a, resolution 2.6Å" /> | ||
'''Structure of the dengue virus 2'O methyltransferase in complex with s-adenosyl homocysteine and ribavirin 5' triphosphate'''<br /> | '''Structure of the dengue virus 2'O methyltransferase in complex with s-adenosyl homocysteine and ribavirin 5' triphosphate'''<br /> | ||
==Overview== | ==Overview== | ||
Ribavirin is one of the few nucleoside analogues currently used in the | 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== | ==About this Structure== | ||
1R6A is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Dengue_virus_type_3 Dengue virus type 3] with SO4, SAH and RVP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | 1R6A is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Dengue_virus_type_3 Dengue virus type 3] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=SAH:'>SAH</scene> and <scene name='pdbligand=RVP:'>RVP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R6A OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Benarroch, D.]] | [[Category: Benarroch, D.]] | ||
[[Category: Canard, B.]] | [[Category: Canard, B.]] | ||
[[Category: Egloff, M | [[Category: Egloff, M P.]] | ||
[[Category: Mulard, L.]] | [[Category: Mulard, L.]] | ||
[[Category: Romette, J | [[Category: Romette, J L.]] | ||
[[Category: RVP]] | [[Category: RVP]] | ||
[[Category: SAH]] | [[Category: SAH]] | ||
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[[Category: ribavirin 5'-triphosphate]] | [[Category: ribavirin 5'-triphosphate]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:47:30 2008'' | ||
