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2p41

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Revision as of 06:21, 11 September 2015

Crystal Structure of Dengue Methyltransferase in Complex with 7MeGpppG2'OMe and S-Adenosyl-L-homocysteine

Structural highlights

2p41 is a 1 chain structure with sequence from Dengue virus 2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , ,
Related:	1l9k, 2p1d, 2p3l, 2p3o, 2p3q, 2p40
Gene:	NSP5 (Dengue virus 2)
Activity:	RNA-directed RNA polymerase, with EC number 2.7.7.48
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Egloff MP, Decroly E, Malet H, Selisko B, Benarroch D, Ferron F, Canard B. Structural and functional analysis of methylation and 5'-RNA sequence requirements of short capped RNAs by the methyltransferase domain of dengue virus NS5. J Mol Biol. 2007 Sep 21;372(3):723-36. Epub 2007 Jul 12. PMID:17686489 doi:http://dx.doi.org/10.1016/j.jmb.2007.07.005

1 Structural highlights
2 Evolutionary Conservation
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2p41"

@@ Line 7: / Line 7: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NSP5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11060 Dengue virus 2])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2p41 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p41 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2p41 RCSB], [http://www.ebi.ac.uk/pdbsum/2p41 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2p41 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p41 OCA], [http://pdbe.org/2p41 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2p41 RCSB], [http://www.ebi.ac.uk/pdbsum/2p41 PDBsum]</span></td></tr>
 </table>
 == Evolutionary Conservation ==
@@ Line 27: / Line 27: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2p41" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

2p41

From Proteopedia

Revision as of 06:21, 11 September 2015

Crystal Structure of Dengue Methyltransferase in Complex with 7MeGpppG2'OMe and S-Adenosyl-L-homocysteine

Structural highlights

Evolutionary Conservation

Publication Abstract from PubMed

References

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