2ydw: Difference between revisions
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==Crystal Structure of the First Bromodomain of Human Brd2 with the inhibitor GW841819X== | ==Crystal Structure of the First Bromodomain of Human Brd2 with the inhibitor GW841819X== | ||
<StructureSection load='2ydw' size='340' side='right' caption='[[2ydw]], [[Resolution|resolution]] 1.90Å' scene=''> | <StructureSection load='2ydw' size='340' side='right'caption='[[2ydw]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2ydw]] is a 3 chain structure with sequence from [ | <table><tr><td colspan='2'>[[2ydw]] is a 3 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=2YDW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YDW FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=WSH:BENZYL+[(4R)-1-METHYL-6-PHENYL-4H-[1,2,4]TRIAZOLO[4,3-A][1,4]BENZODIAZEPIN-4-YL]CARBAMATE'>WSH</scene> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=WSH:BENZYL+[(4R)-1-METHYL-6-PHENYL-4H-[1,2,4]TRIAZOLO[4,3-A][1,4]BENZODIAZEPIN-4-YL]CARBAMATE'>WSH</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2ydw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ydw OCA], [https://pdbe.org/2ydw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ydw RCSB], [https://www.ebi.ac.uk/pdbsum/2ydw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ydw ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/BRD2_HUMAN BRD2_HUMAN] May play a role in spermatogenesis or folliculogenesis (By similarity). Binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling. Regulates transcription of the CCND1 gene. Plays a role in nucleosome assembly.<ref>PMID:18406326</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 2ydw" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
| Line 22: | Line 27: | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Chung | [[Category: Large Structures]] | ||
[[Category: Delves | [[Category: Chung C]] | ||
[[Category: Mirguet | [[Category: Delves C]] | ||
[[Category: Nicodeme | [[Category: Mirguet O]] | ||
[[Category: Woodward | [[Category: Nicodeme E]] | ||
[[Category: Woodward R]] | |||
Latest revision as of 13:50, 20 December 2023
Crystal Structure of the First Bromodomain of Human Brd2 with the inhibitor GW841819XCrystal Structure of the First Bromodomain of Human Brd2 with the inhibitor GW841819X
Structural highlights
FunctionBRD2_HUMAN May play a role in spermatogenesis or folliculogenesis (By similarity). Binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling. Regulates transcription of the CCND1 gene. Plays a role in nucleosome assembly.[1] Publication Abstract from PubMedEpigenetic mechanisms of gene regulation have a profound role in normal development and disease processes. An integral part of this mechanism occurs through lysine acetylation of histone tails which are recognized by bromodomains. While the biological and structural characterization of many bromodomain containing proteins has advanced considerably, the therapeutic tractability of this protein family is only now becoming understood. This paper describes the discovery and molecular characterization of potent (nM) small molecule inhibitors that disrupt the function of the BET family of bromodomains (Brd2, Brd3, and Brd4). By using a combination of phenotypic screening, chemoproteomics, and biophysical studies, we have discovered that the protein-protein interactions between bromodomains and acetylated histones can be antagonized by selective small molecules that bind at the acetylated lysine recognition pocket. X-ray crystal structures of compounds bound into bromodomains of Brd2 and Brd4 elucidate the molecular interactions of binding and explain the precisely defined stereochemistry required for activity. Discovery and Characterization of Small Molecule Inhibitors of the BET Family Bromodomains.,Chung CW, Coste H, White JH, Mirguet O, Wilde J, Gosmini RL, Delves C, Magny SM, Woodward R, Hughes SA, Boursier EV, Flynn H, Bouillot AM, Bamborough P, Brusq JM, Gellibert FJ, Jones EJ, Riou AM, Homes P, Martin SL, Uings IJ, Toum J, Clement CA, Boullay AB, Grimley RL, Blandel FM, Prinjha RK, Lee K, Kirilovsky J, Nicodeme E J Med Chem. 2011 Jun 9;54(11):3827-3838. Epub 2011 May 13. PMID:21568322[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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