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| | == Structural highlights == | | == Structural highlights == |
| | <table><tr><td colspan='2'>[[2vdw]] is a 8 chain structure with sequence from [https://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 [https://proteopedia.org/fgij/fg.htm?mol=2VDW FirstGlance]. <br> | | <table><tr><td colspan='2'>[[2vdw]] is a 8 chain structure with sequence from [https://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 [https://proteopedia.org/fgij/fg.htm?mol=2VDW FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/mRNA_guanylyltransferase mRNA guanylyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.50 2.7.7.50] </span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2vdw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vdw OCA], [https://pdbe.org/2vdw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vdw RCSB], [https://www.ebi.ac.uk/pdbsum/2vdw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vdw ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2vdw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vdw OCA], [https://pdbe.org/2vdw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vdw RCSB], [https://www.ebi.ac.uk/pdbsum/2vdw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vdw ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/MCES_VACCW MCES_VACCW]] 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>
| + | [https://www.uniprot.org/uniprot/MCEL_VACCW MCEL_VACCW] Catalytic subunit of the mRNA capping enzyme which catalyzes three enzymatic reactions: the 5' triphosphate end of the pre-mRNA is hydrolyzed to a diphosphate by RNA 5' triphosphatase; the diphosphate RNA end is capped with GMP by RNA guanylyltransferase and the GpppN cap is methylated by RNA (guanine-N7) methyltransferase. 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:18295814</ref> <ref>PMID:18455214</ref> <ref>PMID:18256245</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:18295814</ref> <ref>PMID:18455214</ref> <ref>PMID:18256245</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: Vaccinia virus]] | | [[Category: Vaccinia virus]] |
| - | [[Category: MRNA guanylyltransferase]]
| + | [[Category: Cusack S]] |
| - | [[Category: Cusack, S]] | + | [[Category: De la Pena M]] |
| - | [[Category: Kyrieleis, O J.P]] | + | [[Category: Kyrieleis OJP]] |
| - | [[Category: Pena, M De la]]
| + | |
| - | [[Category: D1-d12 heterodimer]] | + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Methyl-transferase]]
| + | |
| - | [[Category: Methyltransferase]]
| + | |
| - | [[Category: Mrna capping]]
| + | |
| - | [[Category: Mrna capping enzyme]]
| + | |
| - | [[Category: Mrna processing]]
| + | |
| - | [[Category: Multifunctional enzyme]]
| + | |
| - | [[Category: Nucleotidyltransferase]]
| + | |
| - | [[Category: Poxvirus]]
| + | |
| - | [[Category: Rna metabolism]]
| + | |
| - | [[Category: S-adenosyl homocysteine]]
| + | |
| - | [[Category: S-adenosyl-l-methionine]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
MCEL_VACCW Catalytic subunit of the mRNA capping enzyme which catalyzes three enzymatic reactions: the 5' triphosphate end of the pre-mRNA is hydrolyzed to a diphosphate by RNA 5' triphosphatase; the diphosphate RNA end is capped with GMP by RNA guanylyltransferase and the GpppN cap is methylated by RNA (guanine-N7) methyltransferase. 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
- ↑ 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
- ↑ Zheng S, Shuman S. Structure-function analysis of vaccinia virus mRNA cap (guanine-N7) methyltransferase. RNA. 2008 Apr;14(4):696-705. doi: 10.1261/rna.928208. Epub 2008 Feb 6. PMID:18256245 doi:http://dx.doi.org/10.1261/rna.928208
- ↑ 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
- ↑ Zheng S, Shuman S. Structure-function analysis of vaccinia virus mRNA cap (guanine-N7) methyltransferase. RNA. 2008 Apr;14(4):696-705. doi: 10.1261/rna.928208. Epub 2008 Feb 6. PMID:18256245 doi:http://dx.doi.org/10.1261/rna.928208
- ↑ 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
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