3k5k

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{{Seed}}
 
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[[Image:3k5k.png|left|200px]]
 
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==Discovery of a 2,4-Diamino-7-aminoalkoxy-quinazoline as a Potent Inhibitor of Histone Lysine Methyltransferase, G9a==
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The line below this paragraph, containing "STRUCTURE_3k5k", creates the "Structure Box" on the page.
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<StructureSection load='3k5k' size='340' side='right'caption='[[3k5k]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3k5k]] 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=3K5K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3K5K FirstGlance]. <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]] 1.7&#8491;</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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DXQ:7-[3-(DIMETHYLAMINO)PROPOXY]-6-METHOXY-2-(4-METHYL-1,4-DIAZEPAN-1-YL)-N-(1-METHYLPIPERIDIN-4-YL)QUINAZOLIN-4-AMINE'>DXQ</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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{{STRUCTURE_3k5k| PDB=3k5k | SCENE= }}
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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=3k5k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3k5k OCA], [https://pdbe.org/3k5k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3k5k RCSB], [https://www.ebi.ac.uk/pdbsum/3k5k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3k5k ProSAT]</span></td></tr>
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</table>
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== Function ==
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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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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k5/3k5k_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3k5k ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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SAR exploration of the 2,4-diamino-6,7-dimethoxyquinazoline template led to the discovery of 8 (UNC0224) as a potent and selective G9a inhibitor. A high resolution X-ray crystal structure of the G9a-8 complex, the first cocrystal structure of G9a with a small molecule inhibitor, was obtained. The cocrystal structure validated our binding hypothesis and will enable structure-based design of novel inhibitors. 8 is a useful tool for investigating the biology of G9a and its roles in chromatin remodeling.
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===Discovery of a 2,4-Diamino-7-aminoalkoxy-quinazoline as a Potent Inhibitor of Histone Lysine Methyltransferase, G9a===
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Discovery of a 2,4-diamino-7-aminoalkoxyquinazoline as a potent and selective inhibitor of histone lysine methyltransferase G9a.,Liu F, Chen X, Allali-Hassani A, Quinn AM, Wasney GA, Dong A, Barsyte D, Kozieradzki I, Senisterra G, Chau I, Siarheyeva A, Kireev DB, Jadhav A, Herold JM, Frye SV, Arrowsmith CH, Brown PJ, Simeonov A, Vedadi M, Jin J J Med Chem. 2009 Dec 24;52(24):7950-3. PMID:19891491<ref>PMID:19891491</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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<div class="pdbe-citations 3k5k" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_19891491}}, adds the Publication Abstract to the page
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*[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 19891491 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_19891491}}
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__TOC__
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</StructureSection>
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==About this Structure==
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3K5K is a 2 chains structure with sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3K5K OCA].
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==Reference==
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<ref group="xtra">PMID:19891491</ref><references group="xtra"/>
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[[Category: Histone-lysine N-methyltransferase]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Allali-Hassani,A.]]
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[[Category: Large Structures]]
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[[Category: Arrowsmith,C H.]]
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[[Category: Allali-Hassani A]]
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[[Category: Bochkarev,A.]]
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[[Category: Arrowsmith CH]]
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[[Category: Bountra,C.]]
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[[Category: Bochkarev A]]
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[[Category: Brown,P J.]]
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[[Category: Bountra C]]
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[[Category: Chau,I.]]
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[[Category: Brown PJ]]
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[[Category: Chen,X.]]
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[[Category: Chau I]]
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[[Category: Dong,A.]]
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[[Category: Chen X]]
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[[Category: Edwards,A M.]]
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[[Category: Dong A]]
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[[Category: Frye,S V.]]
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[[Category: Edwards AM]]
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[[Category: Jin,J.]]
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[[Category: Frye SV]]
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[[Category: Liu,F.]]
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[[Category: Jin J]]
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[[Category: Senisterra,G.]]
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[[Category: Liu F]]
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[[Category: Vedadi,M.]]
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[[Category: Senisterra G]]
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[[Category: Wasney,G A.]]
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[[Category: Vedadi M]]
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[[Category: Weigelt,J.]]
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[[Category: Wasney GA]]
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[[Category: Ank repeat]]
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[[Category: Weigelt J]]
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[[Category: Chromatin regulator]]
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[[Category: G9a]]
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[[Category: Histone lysine methyltransferase]]
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[[Category: Metal-binding]]
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[[Category: Methyltransferase]]
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[[Category: Nucleus]]
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[[Category: Phosphoprotein]]
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[[Category: S-adenosyl-l-methionine]]
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[[Category: Sgc]]
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[[Category: Structural genomic]]
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[[Category: Structural genomics consortium]]
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[[Category: Transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Aug 18 11:09:42 2010''
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Current revision

Discovery of a 2,4-Diamino-7-aminoalkoxy-quinazoline as a Potent Inhibitor of Histone Lysine Methyltransferase, G9a

PDB ID 3k5k

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