View source for 5mlj


==Bromodomain of Human GCN5 with 4-bromo-2-methyl-5-(((3R,5R)-1-methyl-5-phenylpiperidin-3-yl)amino)pyridazin-3(2H)-one==
<StructureSection load='5mlj' size='340' side='right' caption='[[5mlj]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5mlj]] 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=5MLJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MLJ FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9ST:4-bromo-2-methyl-5-[[(3~{R},5~{R})-1-methyl-5-phenyl-piperidin-3-yl]amino]pyridazin-3-one'>9ST</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KAT2A, GCN5, GCN5L2, HGCN5 ([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_acetyltransferase Histone acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.48 2.3.1.48] </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=5mlj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mlj OCA], [http://pdbe.org/5mlj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mlj RCSB], [http://www.ebi.ac.uk/pdbsum/5mlj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mlj ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/KAT2A_HUMAN KAT2A_HUMAN]] Functions as a histone acetyltransferase (HAT) to promote transcriptional activation. Acetylation of histones gives a specific tag for epigenetic transcription activation. Has significant histone acetyltransferase activity with core histones, but not with nucleosome core particles. Also acetylates non-histone proteins, such as CEBPB (PubMed:17301242). Component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4. In case of HIV-1 infection, it is recruited by the viral protein Tat. Regulates Tat's transactivating activity and may help inducing chromatin remodeling of proviral genes.<ref>PMID:17301242</ref> <ref>PMID:19103755</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
p300/CREB binding protein associated factor (PCAF/KAT2B) and general control nonderepressible 5 (GCN5/KAT2A) are multidomain proteins that have been implicated in retroviral infection, inflammation pathways, and cancer development. However, outside of viral replication, little is known about the dependence of these effects on the C-terminal bromodomain. Herein, we report GSK4027 as a chemical probe for the PCAF/GCN5 bromodomain, together with GSK4028 as an enantiomeric negative control. The probe was optimized from a weakly potent, nonselective pyridazinone hit to deliver high potency for the PCAF/GCN5 bromodomain, high solubility, cellular target engagement, and &gt;/=18000-fold selectivity over the BET family, together with &gt;/=70-fold selectivity over the wider bromodomain families.

Discovery of a Potent, Cell Penetrant, and Selective p300/CBP-Associated Factor (PCAF)/General Control Nonderepressible 5 (GCN5) Bromodomain Chemical Probe.,Humphreys PG, Bamborough P, Chung CW, Craggs PD, Gordon L, Grandi P, Hayhow TG, Hussain J, Jones KL, Lindon M, Michon AM, Renaux JF, Suckling CJ, Tough DF, Prinjha RK J Med Chem. 2017 Jan 26;60(2):695-709. doi: 10.1021/acs.jmedchem.6b01566. Epub, 2017 Jan 9. PMID:28002667<ref>PMID:28002667</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5mlj" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Histone acetyltransferase]]
[[Category: Human]]
[[Category: Chung, C W]]
[[Category: Antagonist]]
[[Category: Bromodomain]]
[[Category: Epigenetic reader]]
[[Category: Gcn5]]
[[Category: Histone]]
[[Category: Inhibitor]]
[[Category: Kat2a]]
[[Category: Transcription]]