3mo0

From Proteopedia

(Difference between revisions)

Revision as of 08:38, 5 August 2016

Human G9a-like (GLP, also known as EHMT1) in complex with inhibitor E11

Structural highlights

3mo0 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Related:	3fpd, 3mo2, 3mo5
Gene:	EHMT1, EUHMTASE1, KIAA1876, KMT1D (HUMAN)
Activity:	Histone-lysine N-methyltransferase, with EC number 2.1.1.43
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[EHMT1_HUMAN] Defects in EHMT1 are the cause of chromosome 9q subtelomeric deletion syndrome (9q- syndrome) [MIM:610253]. Common features seen in these patients are severe mental retardation, hypotonia, brachy(micro)cephaly, epileptic seizures, flat face with hypertelorism, synophrys, anteverted nares, cupid bow or tented upper lip, everted lower lip, prognathism, macroglossia, conotruncal heart defects, and behavioral problems.

Function

[EHMT1_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 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. During G0 phase, it probably contributes to silencing of MYC- and E2F-responsive genes, suggesting a role in G0/G1 transition in cell cycle. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53.^[1] ^[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Dynamic histone lysine methylation involves the activities of modifying enzymes (writers), enzymes removing modifications (erasers), and readers of the histone code. One common feature of these activities is the recognition of lysines in methylated and unmethylated states, whether they are substrates, reaction products, or binding partners. We applied the concept of adding a lysine mimic to an established inhibitor (BIX-01294) of histone H3 lysine 9 methyltransferases G9a and G9a-like protein by including a 5-aminopentyloxy moiety, which is inserted into the target lysine-binding channel and becomes methylated by G9a-like protein, albeit slowly. The compound enhances its potency in vitro and reduces cell toxicity in vivo. We suggest that adding a lysine or methyl-lysine mimic should be considered in the design of small-molecule inhibitors for other methyl-lysine writers, erasers, and readers.

Adding a lysine mimic in the design of potent inhibitors of histone lysine methyltransferases.,Chang Y, Ganesh T, Horton JR, Spannhoff A, Liu J, Sun A, Zhang X, Bedford MT, Shinkai Y, Snyder JP, Cheng X J Mol Biol. 2010 Jul 2;400(1):1-7. Epub 2010 Apr 29. PMID:20434463^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ogawa H, Ishiguro K, Gaubatz S, Livingston DM, Nakatani Y. A complex with chromatin modifiers that occupies E2F- and Myc-responsive genes in G0 cells. Science. 2002 May 10;296(5570):1132-6. PMID:12004135 doi:10.1126/science.1069861
↑ Huang J, Dorsey J, Chuikov S, Zhang X, Jenuwein T, Reinberg D, Berger SL. G9A and GLP methylate lysine 373 in the tumor suppressor p53. J Biol Chem. 2010 Jan 29. PMID:20118233 doi:M109.062588
↑ Chang Y, Ganesh T, Horton JR, Spannhoff A, Liu J, Sun A, Zhang X, Bedford MT, Shinkai Y, Snyder JP, Cheng X. Adding a lysine mimic in the design of potent inhibitors of histone lysine methyltransferases. J Mol Biol. 2010 Jul 2;400(1):1-7. Epub 2010 Apr 29. PMID:20434463 doi:10.1016/j.jmb.2010.04.048

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3mo0"

@@ Line 1: / Line 1: @@
 ==Human G9a-like (GLP, also known as EHMT1) in complex with inhibitor E11==
 <StructureSection load='3mo0' size='340' side='right' caption='[[3mo0]], [[Resolution|resolution]] 2.78&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3mo0]] is a 2 chain structure with sequence 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=3MO0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3MO0 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3mo0]] 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=3MO0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3MO0 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=E11:N~4~-(1-BENZYLPIPERIDIN-4-YL)-N~2~-[3-(DIMETHYLAMINO)PROPYL]-6,7-DIMETHOXYQUINAZOLINE-2,4-DIAMINE'>E11</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3fpd|3fpd]], [[3mo2|3mo2]], [[3mo5|3mo5]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EHMT1, EUHMTASE1, KIAA1876, KMT1D ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EHMT1, EUHMTASE1, KIAA1876, KMT1D ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone-lysine_N-methyltransferase Histone-lysine N-methyltransferase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3mo0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mo0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3mo0 RCSB], [http://www.ebi.ac.uk/pdbsum/3mo0 PDBsum]</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=3mo0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mo0 OCA], [http://pdbe.org/3mo0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3mo0 RCSB], [http://www.ebi.ac.uk/pdbsum/3mo0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3mo0 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 21: / Line 22: @@
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</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/chain_selection.php?pdb_ID=2ata ConSurf].
+</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=3mo0 ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 31: / Line 32: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3mo0" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 39: / Line 41: @@
 </StructureSection>
 [[Category: Histone-lysine N-methyltransferase]]
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Chang, Y]]
 [[Category: Cheng, X]]

3mo0

From Proteopedia

Revision as of 08:38, 5 August 2016

Human G9a-like (GLP, also known as EHMT1) in complex with inhibitor E11

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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