7cd9

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
==Crystal Structure of SETDB1 tudor domain in complexed with Compound 6==
==Crystal Structure of SETDB1 tudor domain in complexed with Compound 6==
-
<StructureSection load='7cd9' size='340' side='right'caption='[[7cd9]]' scene=''>
+
<StructureSection load='7cd9' size='340' side='right'caption='[[7cd9]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CD9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CD9 FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[7cd9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CD9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CD9 FirstGlance]. <br>
-
</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=7cd9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cd9 OCA], [https://pdbe.org/7cd9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cd9 RCSB], [https://www.ebi.ac.uk/pdbsum/7cd9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cd9 ProSAT]</span></td></tr>
+
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=FVR:3-methyl-2-[[(3R,5R)-1-methyl-5-(4-phenylmethoxyphenyl)piperidin-3-yl]amino]-5H-pyrrolo[3,2-d]pyrimidin-4-one'>FVR</scene></td></tr>
 +
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SETDB1, ESET, KIAA0067, KMT1E ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=7cd9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cd9 OCA], [https://pdbe.org/7cd9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cd9 RCSB], [https://www.ebi.ac.uk/pdbsum/7cd9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cd9 ProSAT]</span></td></tr>
</table>
</table>
 +
== Function ==
 +
[[https://www.uniprot.org/uniprot/SETB1_HUMAN SETB1_HUMAN]] Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3. H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. H3 'Lys-9' trimethylation is coordinated with DNA methylation. Probably forms a complex with MBD1 and ATF7IP that represses transcription and couples DNA methylation and histone 'Lys-9' trimethylation. Its activity is dependent on MBD1 and is heritably maintained through DNA replication by being recruited by CAF-1. SETDB1 is targeted to histone H3 by TRIM28/TIF1B, a factor recruited by KRAB zinc-finger proteins.<ref>PMID:12869583</ref> <ref>PMID:14536086</ref> <ref>PMID:15327775</ref> <ref>PMID:17952062</ref>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
SET domain bifurcated protein 1 (SETDB1) is a histone lysine methyltransferase that promotes the silencing of some tumour suppressor genes and is overexpressed in many cancers. SETDB1 contains a unique tandem tudor domain (TTD) that recognizes histone H3 sequences containing both methylated and acetylated lysines. Beginning with the identification of a hit compound (Cpd1), we discovered the first potent and selective small molecule SETDB1-TTD inhibitor (R,R)-59 through stepwise structure-guided optimization. (R,R)-59 showed a KD value of 0.088+/-0.045 muM in the ITC assay. The high potency of (R,R)-59 was well explained by the cocrystal structure of the (R,R)-59-TTD complex. (R,R)-59 is an endogenous binder competitive inhibitor. Evidence has also demonstrated its cellular target engagement. Interestingly, the enantiomer (S,S)-59 did not show activity in all the assays, highlighting the potential of (R,R)-59 as a tool compound in exploring the biological functions of SETDB1-TTD.
 +
 +
Structure-Guided Discovery of a Potent and Selective Cell-Active Inhibitor of SETDB1 Tudor Domain.,Guo Y, Mao X, Xiong L, Xia A, You J, Lin G, Wu C, Huang L, Wang Y, Yang S Angew Chem Int Ed Engl. 2021 Apr 12;60(16):8760-8765. doi:, 10.1002/anie.202017200. Epub 2021 Mar 8. PMID:33511756<ref>PMID:33511756</ref>
 +
 +
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 +
</div>
 +
<div class="pdbe-citations 7cd9" style="background-color:#fffaf0;"></div>
 +
== References ==
 +
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
 +
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Large Structures]]
-
[[Category: Guo Y]]
+
[[Category: Guo, Y]]
-
[[Category: Huang L]]
+
[[Category: Huang, L]]
-
[[Category: Mao X]]
+
[[Category: Mao, X]]
-
[[Category: Wu C]]
+
[[Category: Wu, C]]
-
[[Category: Xiong L]]
+
[[Category: Xiong, L]]
-
[[Category: Yang S]]
+
[[Category: Yang, S]]
 +
[[Category: Inhibitor]]
 +
[[Category: Setdb1]]
 +
[[Category: Transferase]]
 +
[[Category: Tudor domain]]

Revision as of 07:01, 14 April 2021

Crystal Structure of SETDB1 tudor domain in complexed with Compound 6

PDB ID 7cd9

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7cd9"
Personal tools