4nvq

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==Human G9a in Complex with Inhibitor A-366==
==Human G9a in Complex with Inhibitor A-366==
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<StructureSection load='4nvq' size='340' side='right' caption='[[4nvq]], [[Resolution|resolution]] 2.03&Aring;' scene=''>
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<StructureSection load='4nvq' size='340' side='right'caption='[[4nvq]], [[Resolution|resolution]] 2.03&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4nvq]] 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=4NVQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NVQ FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4nvq]] 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=4NVQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NVQ FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2OD:5-METHOXY-6-[3-(PYRROLIDIN-1-YL)PROPOXY]SPIRO[CYCLOBUTANE-1,3-INDOL]-2-AMINE'>2OD</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.03&#8491;</td></tr>
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<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EHMT2, BAT8, C6orf30, G9A, KMT1C, NG36 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2OD:5-METHOXY-6-[3-(PYRROLIDIN-1-YL)PROPOXY]SPIRO[CYCLOBUTANE-1,3-INDOL]-2-AMINE'>2OD</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4nvq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nvq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4nvq RCSB], [http://www.ebi.ac.uk/pdbsum/4nvq PDBsum]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4nvq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nvq OCA], [https://pdbe.org/4nvq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nvq RCSB], [https://www.ebi.ac.uk/pdbsum/4nvq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nvq ProSAT]</span></td></tr>
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<table>
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</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[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>
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G9a is a histone lysine methyltransferase responsible for the methylation of histone H3 lysine 9. The discovery of A-366 arose from a unique diversity screening hit, which was optimized by incorporation of a propyl-pyrrolidine subunit to occupy the enzyme lysine channel. A-366 is a potent inhibitor of G9a (IC50: 3.3 nM) with greater than 1000-fold selectivity over 21 other methyltransferases.
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Discovery and development of potent and selective inhibitors of histone methyltransferase g9a.,Sweis RF, Pliushchev M, Brown PJ, Guo J, Li F, Maag D, Petros AM, Soni NB, Tse C, Vedadi M, Michaelides MR, Chiang GG, Pappano WN ACS Med Chem Lett. 2014 Jan 2;5(2):205-9. doi: 10.1021/ml400496h. eCollection, 2014 Feb 13. PMID:24900801<ref>PMID:24900801</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==See Also==
==See Also==
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*[[Histone methyltransferase|Histone methyltransferase]]
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*[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
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[[Category: Brown, P J.]]
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[[Category: Large Structures]]
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[[Category: Chiang, G G.]]
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[[Category: Brown PJ]]
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[[Category: Guo, J.]]
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[[Category: Chiang GG]]
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[[Category: Li, F.]]
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[[Category: Guo J]]
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[[Category: Maag, D.]]
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[[Category: Li F]]
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[[Category: Michaelides, M R.]]
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[[Category: Maag D]]
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[[Category: Pappano, W N.]]
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[[Category: Michaelides MR]]
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[[Category: Petros, A M.]]
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[[Category: Pappano WN]]
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[[Category: Pliushchev, M.]]
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[[Category: Petros AM]]
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[[Category: Soni, N B.]]
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[[Category: Pliushchev M]]
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[[Category: Sweis, R F.]]
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[[Category: Soni NB]]
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[[Category: Tse, C.]]
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[[Category: Sweis RF]]
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[[Category: Vedadi, M.]]
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[[Category: Tse C]]
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[[Category: Lysine methyl transferase]]
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[[Category: Vedadi M]]
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[[Category: Transferase-transferase inhibitor complex]]
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Current revision

Human G9a in Complex with Inhibitor A-366

PDB ID 4nvq

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