1l9k
From Proteopedia
(New page: 200px<br /><applet load="1l9k" size="450" color="white" frame="true" align="right" spinBox="true" caption="1l9k, resolution 2.40Å" /> '''dengue methyltransfe...) |
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| - | [[Image:1l9k.gif|left|200px]]<br /><applet load="1l9k" size=" | + | [[Image:1l9k.gif|left|200px]]<br /><applet load="1l9k" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1l9k, resolution 2.40Å" /> | caption="1l9k, resolution 2.40Å" /> | ||
'''dengue methyltransferase'''<br /> | '''dengue methyltransferase'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Viruses represent an attractive system with which to study the molecular | + | Viruses represent an attractive system with which to study the molecular basis of mRNA capping and its relation to the RNA transcription machinery. The RNA-dependent RNA polymerase NS5 of flaviviruses presents a characteristic motif of S-adenosyl-L-methionine-dependent methyltransferases at its N-terminus, and polymerase motifs at its C-terminus. The crystal structure of an N-terminal fragment of Dengue virus type 2 NS5 is reported at 2.4 A resolution. We show that this NS5 domain includes a typical methyltransferase core and exhibits a (nucleoside-2'-O-)-methyltransferase activity on capped RNA. The structure of a ternary complex comprising S-adenosyl-L-homocysteine and a guanosine triphosphate (GTP) analogue shows that 54 amino acids N-terminal to the core provide a novel GTP-binding site that selects guanine using a previously unreported mechanism. Binding studies using GTP- and RNA cap-analogues, as well as the spatial arrangement of the methyltransferase active site relative to the GTP-binding site, suggest that the latter is a specific cap-binding site. As RNA capping is an essential viral function, these results provide a structural basis for the rational design of drugs against the emerging flaviviruses. |
==About this Structure== | ==About this Structure== | ||
| - | 1L9K 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 and SAH 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:// | + | 1L9K 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> and <scene name='pdbligand=SAH:'>SAH</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=1L9K 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: Romette, J | + | [[Category: Romette, J L.]] |
[[Category: Selisko, B.]] | [[Category: Selisko, B.]] | ||
[[Category: SAH]] | [[Category: SAH]] | ||
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[[Category: methyltransferase fold]] | [[Category: methyltransferase fold]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:42:47 2008'' |
Revision as of 11:42, 21 February 2008
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dengue methyltransferase
Overview
Viruses represent an attractive system with which to study the molecular basis of mRNA capping and its relation to the RNA transcription machinery. The RNA-dependent RNA polymerase NS5 of flaviviruses presents a characteristic motif of S-adenosyl-L-methionine-dependent methyltransferases at its N-terminus, and polymerase motifs at its C-terminus. The crystal structure of an N-terminal fragment of Dengue virus type 2 NS5 is reported at 2.4 A resolution. We show that this NS5 domain includes a typical methyltransferase core and exhibits a (nucleoside-2'-O-)-methyltransferase activity on capped RNA. The structure of a ternary complex comprising S-adenosyl-L-homocysteine and a guanosine triphosphate (GTP) analogue shows that 54 amino acids N-terminal to the core provide a novel GTP-binding site that selects guanine using a previously unreported mechanism. Binding studies using GTP- and RNA cap-analogues, as well as the spatial arrangement of the methyltransferase active site relative to the GTP-binding site, suggest that the latter is a specific cap-binding site. As RNA capping is an essential viral function, these results provide a structural basis for the rational design of drugs against the emerging flaviviruses.
About this Structure
1L9K is a Single protein structure of sequence from Dengue virus type 3 with and as ligands. Active as RNA-directed RNA polymerase, with EC number 2.7.7.48 Full crystallographic information is available from OCA.
Reference
An RNA cap (nucleoside-2'-O-)-methyltransferase in the flavivirus RNA polymerase NS5: crystal structure and functional characterization., Egloff MP, Benarroch D, Selisko B, Romette JL, Canard B, EMBO J. 2002 Jun 3;21(11):2757-68. PMID:12032088
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