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| | <StructureSection load='4x41' size='340' side='right'caption='[[4x41]], [[Resolution|resolution]] 3.50Å' scene=''> | | <StructureSection load='4x41' size='340' side='right'caption='[[4x41]], [[Resolution|resolution]] 3.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4x41]] is a 2 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=4X41 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4X41 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4x41]] is a 2 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=4X41 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4X41 FirstGlance]. <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></td></tr> | + | </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></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PRMT8, HRMT1L3, HRMT1L4 ([http://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=4x41 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x41 OCA], [https://pdbe.org/4x41 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4x41 RCSB], [https://www.ebi.ac.uk/pdbsum/4x41 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4x41 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone-arginine_N-methyltransferase Histone-arginine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.125 2.1.1.125] </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=4x41 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x41 OCA], [http://pdbe.org/4x41 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4x41 RCSB], [http://www.ebi.ac.uk/pdbsum/4x41 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4x41 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ANM8_HUMAN ANM8_HUMAN]] Membrane-associated arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and asymmetrical dimethylarginine (aDMA). Able to mono- and dimethylate EWS protein; however its precise role toward EWS remains unclear as it still interacts with fully methylated EWS.<ref>PMID:16051612</ref> <ref>PMID:17925405</ref> <ref>PMID:18320585</ref> | + | [https://www.uniprot.org/uniprot/ANM8_HUMAN ANM8_HUMAN] Membrane-associated arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and asymmetrical dimethylarginine (aDMA). Able to mono- and dimethylate EWS protein; however its precise role toward EWS remains unclear as it still interacts with fully methylated EWS.<ref>PMID:16051612</ref> <ref>PMID:17925405</ref> <ref>PMID:18320585</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: Histone-arginine N-methyltransferase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ho, M C]] | + | [[Category: Ho MC]] |
| - | [[Category: Lee, W C]] | + | [[Category: Lee WC]] |
| - | [[Category: Dimerization]]
| + | |
| - | [[Category: Methylation]]
| + | |
| - | [[Category: Protein arginine methyltransferase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
ANM8_HUMAN Membrane-associated arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and asymmetrical dimethylarginine (aDMA). Able to mono- and dimethylate EWS protein; however its precise role toward EWS remains unclear as it still interacts with fully methylated EWS.[1] [2] [3]
Publication Abstract from PubMed
Type-I protein arginine methyltransferases (PRMTs) catalyze asymmetric dimethylation of various proteins, and their dysregulations often correlate with tumorigenesis or developmental deficiency. Recent studies have focused on the in vivo substrate identification and the enzyme mechanism with peptide substrates. However, how PRMTs recognize substrates at the protein level remain unknown. PRMT8 is one of the least characterized type-I PRMTs and its crystal structure has not been reported. Here, we report the crystal structure of PRMT8:SAH complex, identify a new non-histone protein substrate NIFK, and uncover a previously unknown regulatory region specifically required for recognizing NIFK. Instead of the canonical dimeric structure for other type-I PRMTs, PRMT8 exists as tetramer in solution. Using X-ray crystallography in combination with small angle X-ray scattering experiments, the dimer of dimers architecture where two PRMT8 dimers are held together mainly by beta-strand interactions was proposed. Mutation of PRMT8-beta15 impedes the methylation of NIFK but still allows methylation of histone H2A/H2B dimer or a peptide substrate, suggesting a possible structural basis for recognition of protein substrates. Lastly, we observed two PRMT8 dimer orientations resulting in open (without SAH) and closed (with SAH bound) conformations. The comparison be-tween open and closed conformations may provide useful information for PRMT1/8 inhibitor design.
PROTEIN ARGININE METHYLTRANSFERASE 8: tetrameric structure and protein substrate specificity.,Lee WC, Lin WL, Matsui T, Chen ES, Wei TW, Lin WH, Hu H, Zheng YG, Tsai MD, Ho MC Biochemistry. 2015 Nov 3. PMID:26529540[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lee J, Sayegh J, Daniel J, Clarke S, Bedford MT. PRMT8, a new membrane-bound tissue-specific member of the protein arginine methyltransferase family. J Biol Chem. 2005 Sep 23;280(38):32890-6. Epub 2005 Jul 28. PMID:16051612 doi:http://dx.doi.org/M506944200
- ↑ Sayegh J, Webb K, Cheng D, Bedford MT, Clarke SG. Regulation of protein arginine methyltransferase 8 (PRMT8) activity by its N-terminal domain. J Biol Chem. 2007 Dec 14;282(50):36444-53. Epub 2007 Oct 9. PMID:17925405 doi:http://dx.doi.org/10.1074/jbc.M704650200
- ↑ Pahlich S, Zakaryan RP, Gehring H. Identification of proteins interacting with protein arginine methyltransferase 8: the Ewing sarcoma (EWS) protein binds independent of its methylation state. Proteins. 2008 Sep;72(4):1125-37. doi: 10.1002/prot.22004. PMID:18320585 doi:http://dx.doi.org/10.1002/prot.22004
- ↑ Lee WC, Lin WL, Matsui T, Chen ES, Wei TW, Lin WH, Hu H, Zheng YG, Tsai MD, Ho MC. PROTEIN ARGININE METHYLTRANSFERASE 8: tetrameric structure and protein substrate specificity. Biochemistry. 2015 Nov 3. PMID:26529540 doi:http://dx.doi.org/10.1021/acs.biochem.5b00995
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