4x41
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<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> | <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" id="ligandDat"><scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</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]] 3.5Å</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='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='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> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[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> | [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;"> | ||
| - | == 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. | ||
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| - | 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<ref>PMID:26529540</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4x41" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
Crystal Structure of Protein Arginine Methyltransferase PRMT8
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