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| | <StructureSection load='3egi' size='340' side='right'caption='[[3egi]], [[Resolution|resolution]] 2.21Å' scene=''> | | <StructureSection load='3egi' size='340' side='right'caption='[[3egi]], [[Resolution|resolution]] 2.21Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3egi]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EGI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3EGI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3egi]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EGI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3EGI FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</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]] 2.21Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TGS1, HCA137, NCOA6IP, PIMT ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3egi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3egi OCA], [https://pdbe.org/3egi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3egi RCSB], [https://www.ebi.ac.uk/pdbsum/3egi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3egi 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=3egi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3egi OCA], [https://pdbe.org/3egi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3egi RCSB], [https://www.ebi.ac.uk/pdbsum/3egi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3egi ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/TGS1_HUMAN TGS1_HUMAN]] Catalyzes the 2 serial methylation steps for the conversion of the 7-monomethylguanosine (m(7)G) caps of snRNAs and snoRNAs to a 2,2,7-trimethylguanosine (m(2,2,7)G) cap structure. The enzyme is specific for guanine, and N7 methylation must precede N2 methylation. Hypermethylation of the m7G cap of U snRNAs leads to their concentration in nuclear foci, their colocalization with coilin and the formation of canonical Cajal bodies (CBs). Plays a role in transcriptional regulation.<ref>PMID:11517327</ref> <ref>PMID:11912212</ref> <ref>PMID:16687569</ref> <ref>PMID:18775984</ref>
| + | [https://www.uniprot.org/uniprot/TGS1_HUMAN TGS1_HUMAN] Catalyzes the 2 serial methylation steps for the conversion of the 7-monomethylguanosine (m(7)G) caps of snRNAs and snoRNAs to a 2,2,7-trimethylguanosine (m(2,2,7)G) cap structure. The enzyme is specific for guanine, and N7 methylation must precede N2 methylation. Hypermethylation of the m7G cap of U snRNAs leads to their concentration in nuclear foci, their colocalization with coilin and the formation of canonical Cajal bodies (CBs). Plays a role in transcriptional regulation.<ref>PMID:11517327</ref> <ref>PMID:11912212</ref> <ref>PMID:16687569</ref> <ref>PMID:18775984</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/eg/3egi_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/eg/3egi_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Dickmanns, A]] | + | [[Category: Dickmanns A]] |
| - | [[Category: Ficner, R]] | + | [[Category: Ficner R]] |
| - | [[Category: Monecke, T]] | + | [[Category: Monecke T]] |
| - | [[Category: Alpha-beta-alpha sandwich]]
| + | |
| - | [[Category: Methyltransferase]]
| + | |
| - | [[Category: Methyltransferase-domain]]
| + | |
| - | [[Category: Nucleus]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transcription regulation]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
TGS1_HUMAN Catalyzes the 2 serial methylation steps for the conversion of the 7-monomethylguanosine (m(7)G) caps of snRNAs and snoRNAs to a 2,2,7-trimethylguanosine (m(2,2,7)G) cap structure. The enzyme is specific for guanine, and N7 methylation must precede N2 methylation. Hypermethylation of the m7G cap of U snRNAs leads to their concentration in nuclear foci, their colocalization with coilin and the formation of canonical Cajal bodies (CBs). Plays a role in transcriptional regulation.[1] [2] [3] [4]
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
Methyltransferases play an important role in the post-transcriptional maturation of most ribonucleic acids. The modification of spliceosomal UsnRNAs includes N2-dimethylation of the m(7)G cap catalyzed by trimethylguanosine synthase 1 (TGS1). This 5'-cap hypermethylation occurs during the biogenesis of UsnRNPs as it initiates the m(3)G cap-dependent nuclear import of UsnRNPs. The conserved methyltransferase domain of human TGS1 has been purified, crystallized and the crystal structure of this domain with bound substrate m(7)GpppA was solved by means of multiple-wavelength anomalous dispersion. Crystal structure analysis revealed that m(7)GpppA binds via its adenosine moiety to the structurally conserved adenosylmethionine-binding pocket, while the m(7) guanosine remains unbound. This unexpected binding only occurs in the absence of AdoMet and suggests an incomplete binding pocket for the m(7)G cap which is caused by the N-terminal truncation of the protein. These structural data are consistent with the finding that the crystallized fragment of human TGS1 is catalytically inactive, while a fragment that is 17 amino acids longer exhibits activity.
Structure analysis of the conserved methyltransferase domain of human trimethylguanosine synthase TGS1.,Monecke T, Dickmanns A, Strasser A, Ficner R Acta Crystallogr D Biol Crystallogr. 2009 Apr;65(Pt 4):332-8. Epub 2009 Mar 19. PMID:19307714[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Zhu Y, Qi C, Cao WQ, Yeldandi AV, Rao MS, Reddy JK. Cloning and characterization of PIMT, a protein with a methyltransferase domain, which interacts with and enhances nuclear receptor coactivator PRIP function. Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10380-5. Epub 2001 Aug 21. PMID:11517327 doi:http://dx.doi.org/10.1073/pnas.181347498
- ↑ Misra P, Qi C, Yu S, Shah SH, Cao WQ, Rao MS, Thimmapaya B, Zhu Y, Reddy JK. Interaction of PIMT with transcriptional coactivators CBP, p300, and PBP differential role in transcriptional regulation. J Biol Chem. 2002 May 31;277(22):20011-9. Epub 2002 Mar 23. PMID:11912212 doi:http://dx.doi.org/10.1074/jbc.M201739200
- ↑ Lemm I, Girard C, Kuhn AN, Watkins NJ, Schneider M, Bordonne R, Luhrmann R. Ongoing U snRNP biogenesis is required for the integrity of Cajal bodies. Mol Biol Cell. 2006 Jul;17(7):3221-31. Epub 2006 May 10. PMID:16687569 doi:http://dx.doi.org/10.1091/mbc.E06-03-0247
- ↑ Hausmann S, Zheng S, Costanzo M, Brost RL, Garcin D, Boone C, Shuman S, Schwer B. Genetic and biochemical analysis of yeast and human cap trimethylguanosine synthase: functional overlap of 2,2,7-trimethylguanosine caps, small nuclear ribonucleoprotein components, pre-mRNA splicing factors, and RNA decay pathways. J Biol Chem. 2008 Nov 14;283(46):31706-18. doi: 10.1074/jbc.M806127200. Epub 2008, Sep 5. PMID:18775984 doi:http://dx.doi.org/10.1074/jbc.M806127200
- ↑ Monecke T, Dickmanns A, Strasser A, Ficner R. Structure analysis of the conserved methyltransferase domain of human trimethylguanosine synthase TGS1. Acta Crystallogr D Biol Crystallogr. 2009 Apr;65(Pt 4):332-8. Epub 2009 Mar 19. PMID:19307714 doi:10.1107/S0907444909003102
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