7cjt

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (16:09, 29 November 2023) (edit) (undo)
 
(One intermediate revision not shown.)
Line 1: Line 1:
-
'''Unreleased structure'''
 
-
The entry 7cjt is ON HOLD until Paper Publication
+
==Crystal Structure of SETDB1 Tudor domain in complexed with (R,R)-59==
 +
<StructureSection load='7cjt' size='340' side='right'caption='[[7cjt]], [[Resolution|resolution]] 2.47&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[7cjt]] is a 4 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=7CJT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CJT FirstGlance]. <br>
 +
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.474&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=G09:2-[[(3~{R},5~{R})-1-methyl-5-(4-phenylmethoxyphenyl)piperidin-3-yl]amino]-3-prop-2-enyl-5~{H}-pyrrolo[3,2-d]pyrimidin-4-one'>G09</scene></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=7cjt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cjt OCA], [https://pdbe.org/7cjt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cjt RCSB], [https://www.ebi.ac.uk/pdbsum/7cjt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cjt ProSAT]</span></td></tr>
 +
</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.
-
Authors:
+
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>
-
Description:
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
[[Category: Unreleased Structures]]
+
</div>
 +
<div class="pdbe-citations 7cjt" style="background-color:#fffaf0;"></div>
 +
 
 +
==See Also==
 +
*[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]]
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
 +
[[Category: Homo sapiens]]
 +
[[Category: Large Structures]]
 +
[[Category: Guo YP]]
 +
[[Category: Liang X]]
 +
[[Category: Luyi H]]
 +
[[Category: Mao X]]
 +
[[Category: Wu C]]
 +
[[Category: Yang S]]

Current revision

Crystal Structure of SETDB1 Tudor domain in complexed with (R,R)-59

PDB ID 7cjt

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/7cjt"
Personal tools