2p1d
From Proteopedia
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'''Crystal structure of dengue methyltransferase in complex with GTP and S-Adenosyl-L-homocysteine''' | '''Crystal structure of dengue methyltransferase in complex with GTP and S-Adenosyl-L-homocysteine''' | ||
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[[Category: Egloff, M P.]] | [[Category: Egloff, M P.]] | ||
[[Category: MSGP, Marseilles Structural Genomics Program.@.AFMB.]] | [[Category: MSGP, Marseilles Structural Genomics Program.@.AFMB.]] | ||
| - | [[Category: | + | [[Category: Dengue virus methyltransferase]] |
| - | [[Category: | + | [[Category: Marseilles structural genomics program @ afmb]] |
| - | [[Category: | + | [[Category: Msgp]] |
| - | [[Category: | + | [[Category: Structural genomic]] |
| - | [[Category: | + | [[Category: Viral enzymes involved in replication]] |
| - | [[Category: | + | [[Category: Vizier]] |
| - | [[Category: | + | [[Category: Vizier. viral enzymes involved in replication]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 12:08:01 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 09:08, 4 May 2008
Crystal structure of dengue methyltransferase in complex with GTP and S-Adenosyl-L-homocysteine
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
2P1D is a Single protein structure of sequence from Dengue virus 2. 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 Page seeded by OCA on Sun May 4 12:08:01 2008
Categories: Dengue virus 2 | RNA-directed RNA polymerase | Single protein | Benarooch, D. | Egloff, M P. | MSGP, Marseilles Structural Genomics Program.@.AFMB. | Dengue virus methyltransferase | Marseilles structural genomics program @ afmb | Msgp | Structural genomic | Viral enzymes involved in replication | Vizier | Vizier. viral enzymes involved in replication
