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2vdw

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Revision as of 18:07, 24 December 2014

GUANOSINE N7 METHYL-TRANSFERASE SUB-COMPLEX (D1-D12) OF THE VACCINIA VIRUS MRNA CAPPING ENZYME

Structural highlights

2vdw is a 8 chain structure with sequence from Vaccinia virus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Activity:	mRNA guanylyltransferase, with EC number 2.7.7.50
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[MCES_VACCV] Regulatory subunit of the mRNA cap enzyme which stabilizes the catalytic subunit and enhances its methyltransferase activity through an allosteric mechanism. Heterodimeric mRNA capping enzyme catalyzes the linkage of a N7-methyl-guanosine moiety to the first transcribed nucleotide (cap 0 structure), whereas the polymerase associated VP39 is responsible for a second methylation at the 2'-O position of the ribose (cap 1 structure).^[1] ^[2] ^[3] The heterodimeric enzyme is also involved in early viral gene transcription termination and intermediate viral gene transcription initiation. Early gene transcription termination requires the termination factor VTF, the DNA-dependent ATPase NPH-I and the Rap94 subunit of the viral RNA polymerase, as well as the presence of a specific termination motif. Binds, together with RAP94, to the termination motif 5'-UUUUUNU-3' in the nascent early mRNA.^[4] ^[5] ^[6]

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 vaccinia virus mRNA capping enzyme is a multifunctional heterodimeric protein associated with the viral polymerase that both catalyses the three steps of mRNA capping and regulates gene transcription. The structure of a subcomplex comprising the C-terminal N7-methyl-transferase (MT) domain of the large D1 subunit, the stimulatory D12 subunit and bound S-adenosyl-homocysteine (AdoHcy) has been determined at 2.7 A resolution and reveals several novel features of the poxvirus capping enzyme. The structure shows for the first time the critical role played by the proteolytically sensitive N-terminus of the MT domain in binding the methyl donor and in catalysis. In addition, the poxvirus enzyme has a completely unique mode of binding of the adenosine moiety of AdoHcy, a feature that could be exploited for design of specific anti-poxviral compounds. The structure of the poxvirus-specific D12 subunit suggests that it was originally an RNA cap 2'O-MT that has evolved to a catalytically inactive form that has been retained for D1 stabilisation and MT activity enhancement through an allosteric mechanism.

Structural insights into the mechanism and evolution of the vaccinia virus mRNA cap N7 methyl-transferase.,De la Pena M, Kyrieleis OJ, Cusack S EMBO J. 2007 Nov 28;26(23):4913-25. Epub 2007 Nov 8. PMID:17989694^[7]

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

References

↑ Niles EG, Lee-Chen GJ, Shuman S, Moss B, Broyles SS. Vaccinia virus gene D12L encodes the small subunit of the viral mRNA capping enzyme. Virology. 1989 Oct;172(2):513-22. PMID:2552660
↑ Shatzer AN, Kato SE, Condit RC. Phenotypic analysis of a temperature sensitive mutant in the large subunit of the vaccinia virus mRNA capping enzyme. Virology. 2008 May 25;375(1):236-52. doi: 10.1016/j.virol.2008.01.028. Epub 2008 , Mar 4. PMID:18295814 doi:http://dx.doi.org/10.1016/j.virol.2008.01.028
↑ Christen LA, Piacente S, Mohamed MR, Niles EG. Vaccinia virus early gene transcription termination factors VTF and Rap94 interact with the U9 termination motif in the nascent RNA in a transcription ternary complex. Virology. 2008 Jun 20;376(1):225-35. doi: 10.1016/j.virol.2008.03.031. Epub 2008 , May 1. PMID:18455214 doi:http://dx.doi.org/10.1016/j.virol.2008.03.031
↑ Niles EG, Lee-Chen GJ, Shuman S, Moss B, Broyles SS. Vaccinia virus gene D12L encodes the small subunit of the viral mRNA capping enzyme. Virology. 1989 Oct;172(2):513-22. PMID:2552660
↑ Shatzer AN, Kato SE, Condit RC. Phenotypic analysis of a temperature sensitive mutant in the large subunit of the vaccinia virus mRNA capping enzyme. Virology. 2008 May 25;375(1):236-52. doi: 10.1016/j.virol.2008.01.028. Epub 2008 , Mar 4. PMID:18295814 doi:http://dx.doi.org/10.1016/j.virol.2008.01.028
↑ Christen LA, Piacente S, Mohamed MR, Niles EG. Vaccinia virus early gene transcription termination factors VTF and Rap94 interact with the U9 termination motif in the nascent RNA in a transcription ternary complex. Virology. 2008 Jun 20;376(1):225-35. doi: 10.1016/j.virol.2008.03.031. Epub 2008 , May 1. PMID:18455214 doi:http://dx.doi.org/10.1016/j.virol.2008.03.031
↑ De la Pena M, Kyrieleis OJ, Cusack S. Structural insights into the mechanism and evolution of the vaccinia virus mRNA cap N7 methyl-transferase. EMBO J. 2007 Nov 28;26(23):4913-25. Epub 2007 Nov 8. PMID:17989694

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2vdw]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Vaccinia_virus Vaccinia virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VDW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2VDW FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/mRNA_guanylyltransferase mRNA guanylyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.50 2.7.7.50] </span></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/mRNA_guanylyltransferase mRNA guanylyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.50 2.7.7.50] </span></td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2vdw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vdw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2vdw RCSB], [http://www.ebi.ac.uk/pdbsum/2vdw 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=2vdw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vdw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2vdw RCSB], [http://www.ebi.ac.uk/pdbsum/2vdw PDBsum]</span></td></tr>
-<table>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/MCES_VACCV MCES_VACCV]] Regulatory subunit of the mRNA cap enzyme which stabilizes the catalytic subunit and enhances its methyltransferase activity through an allosteric mechanism. Heterodimeric mRNA capping enzyme catalyzes the linkage of a N7-methyl-guanosine moiety to the first transcribed nucleotide (cap 0 structure), whereas the polymerase associated VP39 is responsible for a second methylation at the 2'-O position of the ribose (cap 1 structure).<ref>PMID:2552660</ref> <ref>PMID:18295814</ref> <ref>PMID:18455214</ref>   The heterodimeric enzyme is also involved in early viral gene transcription termination and intermediate viral gene transcription initiation. Early gene transcription termination requires the termination factor VTF, the DNA-dependent ATPase NPH-I and the Rap94 subunit of the viral RNA polymerase, as well as the presence of a specific termination motif. Binds, together with RAP94, to the termination motif 5'-UUUUUNU-3' in the nascent early mRNA.<ref>PMID:2552660</ref> <ref>PMID:18295814</ref> <ref>PMID:18455214</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 31: / Line 33: @@
 [[Category: Vaccinia virus]]
 [[Category: MRNA guanylyltransferase]]
-[[Category: Cusack, S.]]
+[[Category: Cusack, S]]
-[[Category: Kyrieleis, O J.P.]]
+[[Category: Kyrieleis, O J.P]]
-[[Category: Pena, M De La.]]
+[[Category: Pena, M De La]]
 [[Category: D1-d12 heterodimer]]
 [[Category: Hydrolase]]

2vdw

From Proteopedia

Revision as of 18:07, 24 December 2014

GUANOSINE N7 METHYL-TRANSFERASE SUB-COMPLEX (D1-D12) OF THE VACCINIA VIRUS MRNA CAPPING ENZYME

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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