3rjw: Difference between revisions

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<StructureSection load='3rjw' size='340' side='right'caption='[[3rjw]], [[Resolution|resolution]] 2.56&Aring;' scene=''>
<StructureSection load='3rjw' size='340' side='right'caption='[[3rjw]], [[Resolution|resolution]] 2.56&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3rjw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3nni 3nni]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RJW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RJW FirstGlance]. <br>
<table><tr><td colspan='2'>[[3rjw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3nni 3nni]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RJW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RJW FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIQ:2-CYCLOHEXYL-6-METHOXY-N-[1-(1-METHYLETHYL)PIPERIDIN-4-YL]-7-(3-PYRROLIDIN-1-YLPROPOXY)QUINAZOLIN-4-AMINE'>CIQ</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.56&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EHMT2, BAT8, C6orf30, G9A, KMT1C, NG36 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIQ:2-CYCLOHEXYL-6-METHOXY-N-[1-(1-METHYLETHYL)PIPERIDIN-4-YL]-7-(3-PYRROLIDIN-1-YLPROPOXY)QUINAZOLIN-4-AMINE'>CIQ</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Histone-lysine_N-methyltransferase Histone-lysine N-methyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.43 2.1.1.43] </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=3rjw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rjw OCA], [https://pdbe.org/3rjw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rjw RCSB], [https://www.ebi.ac.uk/pdbsum/3rjw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rjw 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=3rjw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rjw OCA], [https://pdbe.org/3rjw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rjw RCSB], [https://www.ebi.ac.uk/pdbsum/3rjw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rjw ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/EHMT2_HUMAN EHMT2_HUMAN]] Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones. Also mediates monomethylation of 'Lys-56' of histone H3 (H3K56me1) in G1 phase, leading to promote interaction between histone H3 and PCNA and regulating DNA replication. Also weakly methylates 'Lys-27' of histone H3 (H3K27me). Also required for DNA methylation, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently. Probably targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX and/or DP1. May also methylate histone H1. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53. Also methylates CDYL, WIZ, ACIN1, DNMT1, HDAC1, ERCC6, KLF12 and itself.<ref>PMID:8457211</ref> <ref>PMID:11316813</ref> <ref>PMID:18438403</ref> <ref>PMID:20118233</ref> <ref>PMID:22387026</ref> 
[https://www.uniprot.org/uniprot/EHMT2_HUMAN EHMT2_HUMAN] Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones. Also mediates monomethylation of 'Lys-56' of histone H3 (H3K56me1) in G1 phase, leading to promote interaction between histone H3 and PCNA and regulating DNA replication. Also weakly methylates 'Lys-27' of histone H3 (H3K27me). Also required for DNA methylation, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently. Probably targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX and/or DP1. May also methylate histone H1. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53. Also methylates CDYL, WIZ, ACIN1, DNMT1, HDAC1, ERCC6, KLF12 and itself.<ref>PMID:8457211</ref> <ref>PMID:11316813</ref> <ref>PMID:18438403</ref> <ref>PMID:20118233</ref> <ref>PMID:22387026</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Protein lysine methyltransferases G9a and GLP modulate the transcriptional repression of a variety of genes via dimethylation of Lys9 on histone H3 (H3K9me2) as well as dimethylation of non-histone targets. Here we report the discovery of UNC0638, an inhibitor of G9a and GLP with excellent potency and selectivity over a wide range of epigenetic and non-epigenetic targets. UNC0638 treatment of a variety of cell lines resulted in lower global H3K9me2 levels, equivalent to levels observed for small hairpin RNA knockdown of G9a and GLP with the functional potency of UNC0638 being well separated from its toxicity. UNC0638 markedly reduced the clonogenicity of MCF7 cells, reduced the abundance of H3K9me2 marks at promoters of known G9a-regulated endogenous genes and disproportionately affected several genomic loci encoding microRNAs. In mouse embryonic stem cells, UNC0638 reactivated G9a-silenced genes and a retroviral reporter gene in a concentration-dependent manner without promoting differentiation.
 
A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells.,Vedadi M, Barsyte-Lovejoy D, Liu F, Rival-Gervier S, Allali-Hassani A, Labrie V, Wigle TJ, Dimaggio PA, Wasney GA, Siarheyeva A, Dong A, Tempel W, Wang SC, Chen X, Chau I, Mangano TJ, Huang XP, Simpson CD, Pattenden SG, Norris JL, Kireev DB, Tripathy A, Edwards A, Roth BL, Janzen WP, Garcia BA, Petronis A, Ellis J, Brown PJ, Frye SV, Arrowsmith CH, Jin J Nat Chem Biol. 2011 Jul 10;7(8):566-74. doi: 10.1038/nchembio.599. PMID:21743462<ref>PMID:21743462</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3rjw" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Histone-lysine N-methyltransferase]]
[[Category: Homo sapiens]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Allali-Hassani, A]]
[[Category: Allali-Hassani A]]
[[Category: Arora, K]]
[[Category: Arora K]]
[[Category: Arrowsmith, C H]]
[[Category: Arrowsmith CH]]
[[Category: Barsyte, D]]
[[Category: Barsyte D]]
[[Category: Bochkarev, A]]
[[Category: Bochkarev A]]
[[Category: Bountra, C]]
[[Category: Bountra C]]
[[Category: Brown, P J]]
[[Category: Brown PJ]]
[[Category: Chau, I]]
[[Category: Chau I]]
[[Category: Chavda, N]]
[[Category: Chavda N]]
[[Category: Chen, X]]
[[Category: Chen X]]
[[Category: Dong, A]]
[[Category: Dong A]]
[[Category: Edwards, A M]]
[[Category: Edwards AM]]
[[Category: Frye, S V]]
[[Category: Frye SV]]
[[Category: Hajian, T]]
[[Category: Hajian T]]
[[Category: Herold, J M]]
[[Category: Herold JM]]
[[Category: Jin, J]]
[[Category: Jin J]]
[[Category: Kireev, D B]]
[[Category: Kireev DB]]
[[Category: Liu, F]]
[[Category: Liu F]]
[[Category: Structural genomic]]
[[Category: Senisterra G]]
[[Category: Senisterra, G]]
[[Category: Siarheyeva A]]
[[Category: Siarheyeva, A]]
[[Category: Tempel W]]
[[Category: Tempel, W]]
[[Category: Vedadi M]]
[[Category: Vedadi, M]]
[[Category: Wasney GA]]
[[Category: Wasney, G A]]
[[Category: Weigelt J]]
[[Category: Weigelt, J]]
[[Category: Chemical probe]]
[[Category: Methyltransferase inhibitor]]
[[Category: Sgc]]
[[Category: Transferase-transferase inhibitor complex]]
Retrieved from "https://proteopedia.org/3rjw"