2p1d | pdb_00002p1d
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| 2p1d, resolution 2.90Å | |||||||||||||
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| Ligands: | SO4, SAH and 5GP | ||||||||||||
| Gene: | NSP5 (Dengue virus type 3) | ||||||||||||
| Activity: | RNA-directed RNA polymerase, with EC number 2.7.7.48 | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
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 type 3. 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 Thu Mar 20 18:07:15 2008
Proteopedia Page Contributors and Editors (what is this?)
- Pages with broken file links
- Dengue virus type 3
- RNA-directed RNA polymerase
- Single protein
- Benarooch, D.
- Egloff, M P.
- MSGP, Marseilles Structural Genomics Program.@.AFMB.
- 5GP
- SAH
- SO4
- Vizier. viral enzymes involved in replication
- Vizier; viral enzymes involved in replication; dengue virus methyltransferase; structural genomics; marseilles structural genomics program @ afmb; msgp
