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| | ==Cap-specific mRNA (nucleoside-2'-O-)-methyltransferase 1 Protein in complex with capped RNA fragment== | | ==Cap-specific mRNA (nucleoside-2'-O-)-methyltransferase 1 Protein in complex with capped RNA fragment== |
| - | <StructureSection load='4n48' size='340' side='right' caption='[[4n48]], [[Resolution|resolution]] 2.70Å' scene=''> | + | <StructureSection load='4n48' size='340' side='right'caption='[[4n48]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4n48]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4N48 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4N48 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4n48]] 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=4N48 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4N48 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MGT:7N-METHYL-8-HYDROGUANOSINE-5-TRIPHOSPHATE'>MGT</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MGT:7N-METHYL-8-HYDROGUANOSINE-5-TRIPHOSPHATE'>MGT</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4n49|4n49]], [[4n4a|4n4a]]</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=4n48 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n48 OCA], [https://pdbe.org/4n48 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4n48 RCSB], [https://www.ebi.ac.uk/pdbsum/4n48 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4n48 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FTSJD2, KIAA0082, MTR1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/mRNA_(nucleoside-2'-O)-methyltransferase mRNA (nucleoside-2'-O)-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.57 2.1.1.57] </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=4n48 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n48 OCA], [http://pdbe.org/4n48 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4n48 RCSB], [http://www.ebi.ac.uk/pdbsum/4n48 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4n48 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/CMTR1_HUMAN CMTR1_HUMAN] S-adenosyl-L-methionine-dependent methyltransferase that mediates mRNA cap1 2'-O-ribose methylation to the 5'-cap structure of mRNAs. Methylates the ribose of the first nucleotide of a m(7)GpppG-capped mRNA and small nuclear RNA (snRNA) to produce m(7)GpppRm (cap1). Displays a preference for cap0 transcripts. Cap1 modification is linked to higher levels of translation. May be involved in the interferon response pathway.<ref>PMID:18533109</ref> <ref>PMID:20713356</ref> <ref>PMID:21310715</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Bujnicki, J M]] | + | [[Category: Large Structures]] |
| - | [[Category: Darzynkiewicz, E]] | + | [[Category: Bujnicki JM]] |
| - | [[Category: Kaminska, K H]] | + | [[Category: Darzynkiewicz E]] |
| - | [[Category: Nowotny, M]] | + | [[Category: Kaminska KH]] |
| - | [[Category: Purta, E]] | + | [[Category: Nowotny M]] |
| - | [[Category: Smietanski, M]] | + | [[Category: Purta E]] |
| - | [[Category: Stepinski, J]] | + | [[Category: Smietanski M]] |
| - | [[Category: Werener, M]] | + | [[Category: Stepinski J]] |
| - | [[Category: Capped mrna]]
| + | [[Category: Werener M]] |
| - | [[Category: Methyltransferase]]
| + | |
| - | [[Category: Mrna cap methylation]]
| + | |
| - | [[Category: Transferase-rna complex]]
| + | |
| Structural highlights
Function
CMTR1_HUMAN S-adenosyl-L-methionine-dependent methyltransferase that mediates mRNA cap1 2'-O-ribose methylation to the 5'-cap structure of mRNAs. Methylates the ribose of the first nucleotide of a m(7)GpppG-capped mRNA and small nuclear RNA (snRNA) to produce m(7)GpppRm (cap1). Displays a preference for cap0 transcripts. Cap1 modification is linked to higher levels of translation. May be involved in the interferon response pathway.[1] [2] [3]
Publication Abstract from PubMed
The 5' cap of human messenger RNA contains 2'-O-methylation of the first and often second transcribed nucleotide that is important for its processing, translation and stability. Human enzymes that methylate these nucleotides, termed CMTr1 and CMTr2, respectively, have recently been identified. However, the structures of these enzymes and their mechanisms of action remain unknown. In the present study, we solve the crystal structures of the active CMTr1 catalytic domain in complex with a methyl group donor and a capped oligoribonucleotide, thereby revealing the mechanism of specific recognition of capped RNA. This mechanism differs significantly from viral enzymes, thus providing a framework for their specific targeting. Based on the crystal structure of CMTr1, a comparative model of the CMTr2 catalytic domain is generated. This model, together with mutational analysis, leads to the identification of residues involved in RNA and methyl group donor binding.
Structural analysis of human 2'-O-ribose methyltransferases involved in mRNA cap structure formation.,Smietanski M, Werner M, Purta E, Kaminska KH, Stepinski J, Darzynkiewicz E, Nowotny M, Bujnicki JM Nat Commun. 2014 Jan 9;5:3004. doi: 10.1038/ncomms4004. PMID:24402442[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Haline-Vaz T, Silva TC, Zanchin NI. The human interferon-regulated ISG95 protein interacts with RNA polymerase II and shows methyltransferase activity. Biochem Biophys Res Commun. 2008 Aug 8;372(4):719-24. doi: , 10.1016/j.bbrc.2008.05.137. Epub 2008 Jun 3. PMID:18533109 doi:http://dx.doi.org/10.1016/j.bbrc.2008.05.137
- ↑ Belanger F, Stepinski J, Darzynkiewicz E, Pelletier J. Characterization of hMTr1, a human Cap1 2'-O-ribose methyltransferase. J Biol Chem. 2010 Oct 22;285(43):33037-33044. doi: 10.1074/jbc.M110.155283. Epub , 2010 Aug 16. PMID:20713356 doi:http://dx.doi.org/10.1074/jbc.M110.155283
- ↑ Werner M, Purta E, Kaminska KH, Cymerman IA, Campbell DA, Mittra B, Zamudio JR, Sturm NR, Jaworski J, Bujnicki JM. 2'-O-ribose methylation of cap2 in human: function and evolution in a horizontally mobile family. Nucleic Acids Res. 2011 Jun;39(11):4756-68. doi: 10.1093/nar/gkr038. Epub 2011 , Feb 9. PMID:21310715 doi:http://dx.doi.org/10.1093/nar/gkr038
- ↑ Smietanski M, Werner M, Purta E, Kaminska KH, Stepinski J, Darzynkiewicz E, Nowotny M, Bujnicki JM. Structural analysis of human 2'-O-ribose methyltransferases involved in mRNA cap structure formation. Nat Commun. 2014 Jan 9;5:3004. doi: 10.1038/ncomms4004. PMID:24402442 doi:http://dx.doi.org/10.1038/ncomms4004
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