2p3l
From Proteopedia
| Line 4: | Line 4: | ||
|PDB= 2p3l |SIZE=350|CAPTION= <scene name='initialview01'>2p3l</scene>, resolution 2.20Å | |PDB= 2p3l |SIZE=350|CAPTION= <scene name='initialview01'>2p3l</scene>, resolution 2.20Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=G3A:GUANOSINE-P3-ADENOSINE-5',5'-TRIPHOSPHATE'>G3A</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
| - | |GENE= NSP5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id= | + | |GENE= NSP5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11060 Dengue virus 2]) |
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1l9k|1L9K]], [[2p1d|2P1D]], [[2p3o|2P3O]], [[2p3q|2P3Q]], [[2p40|2P40]], [[2p41|2P41]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2p3l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p3l OCA], [http://www.ebi.ac.uk/pdbsum/2p3l PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2p3l RCSB]</span> | ||
}} | }} | ||
| Line 16: | Line 19: | ||
==About this Structure== | ==About this Structure== | ||
| - | 2P3L is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/ | + | 2P3L is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Dengue_virus_2 Dengue virus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P3L OCA]. |
==Reference== | ==Reference== | ||
Structural and functional analysis of methylation and 5'-RNA sequence requirements of short capped RNAs by the methyltransferase domain of dengue virus NS5., Egloff MP, Decroly E, Malet H, Selisko B, Benarroch D, Ferron F, Canard B, J Mol Biol. 2007 Sep 21;372(3):723-36. Epub 2007 Jul 12. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17686489 17686489] | Structural and functional analysis of methylation and 5'-RNA sequence requirements of short capped RNAs by the methyltransferase domain of dengue virus NS5., Egloff MP, Decroly E, Malet H, Selisko B, Benarroch D, Ferron F, Canard B, J Mol Biol. 2007 Sep 21;372(3):723-36. Epub 2007 Jul 12. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17686489 17686489] | ||
| - | [[Category: Dengue virus | + | [[Category: Dengue virus 2]] |
[[Category: RNA-directed RNA polymerase]] | [[Category: RNA-directed RNA polymerase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[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: viral protein,transferase]] | |
| - | [[Category: viral protein]] | + | [[Category: vizier]] |
| - | [[Category: vizier | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:28:37 2008'' |
Revision as of 01:28, 31 March 2008
| |||||||
| , resolution 2.20Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , , | ||||||
| Gene: | NSP5 (Dengue virus 2) | ||||||
| Activity: | RNA-directed RNA polymerase, with EC number 2.7.7.48 | ||||||
| Related: | 1L9K, 2P1D, 2P3O, 2P3Q, 2P40, 2P41
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of Dengue Methyltransferase in Complex with GpppA and S-Adenosyl-L-Homocysteine
Overview
The N-terminal 33 kDa domain of non-structural protein 5 (NS5) of dengue virus (DV), named NS5MTase(DV), is involved in two of four steps required for the formation of the viral mRNA cap (7Me)GpppA(2'OMe), the guanine-N7 and the adenosine-2'O methylation. Its S-adenosyl-l-methionine (AdoMet) dependent 2'O-methyltransferase (MTase) activity has been shown on capped (7Me+/-)GpppAC(n) RNAs. Here we report structural and binding studies using cap analogues and capped RNAs. We have solved five crystal structures at 1.8 A to 2.8 A resolution of NS5MTase(DV) in complex with cap analogues and the co-product of methylation S-adenosyl-l-homocysteine (AdoHcy). The cap analogues can adopt several conformations. The guanosine moiety of all cap analogues occupies a GTP-binding site identified earlier, indicating that GTP and cap share the same binding site. Accordingly, we show that binding of (7Me)GpppAC(4) and (7Me)GpppAC(5) RNAs is inhibited in the presence of GTP, (7Me)GTP and (7Me)GpppA but not by ATP. This particular position of the cap is in accordance with the 2'O-methylation step. A model was generated of a ternary 2'O-methylation complex of NS5MTase(DV), (7Me)GpppA and AdoMet. RNA-binding increased when (7Me+/-)GpppAGC(n-1) starting with the consensus sequence GpppAG, was used instead of (7Me+/-)GpppAC(n). In the NS5MTase(DV)-GpppA complex the cap analogue adopts a folded, stacked conformation uniquely possible when adenine is the first transcribed nucleotide at the 5' end of nascent RNA, as it is the case in all flaviviruses. This conformation cannot be a functional intermediate of methylation, since both the guanine-N7 and adenosine-2'O positions are too far away from AdoMet. We hypothesize that this conformation mimics the reaction product of a yet-to-be-demonstrated guanylyltransferase activity. A putative Flavivirus RNA capping pathway is proposed combining the different steps where the NS5MTase domain is involved.
About this Structure
2P3L is a Single protein structure of sequence from Dengue virus 2. Full crystallographic information is available from OCA.
Reference
Structural and functional analysis of methylation and 5'-RNA sequence requirements of short capped RNAs by the methyltransferase domain of dengue virus NS5., Egloff MP, Decroly E, Malet H, Selisko B, Benarroch D, Ferron F, Canard B, J Mol Biol. 2007 Sep 21;372(3):723-36. Epub 2007 Jul 12. PMID:17686489
Page seeded by OCA on Mon Mar 31 04:28:37 2008
Categories: Dengue virus 2 | RNA-directed RNA polymerase | Single protein | 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 | Viral protein,transferase | Vizier
