View source for 5mkx


==1.68A STRUCTURE PCAF BROMODOMAIN WITH 4-chloro-2-methyl-5-(methylamino)pyridazin-3(2H)-one==
<StructureSection load='5mkx' size='340' side='right'caption='[[5mkx]], [[Resolution|resolution]] 1.68&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5mkx]] is a 2 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=5MKX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MKX 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]] 1.68&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=82I:4-chloranyl-2-methyl-5-(methylamino)pyridazin-3-one'>82I</scene>, <scene name='pdbligand=BU1:1,4-BUTANEDIOL'>BU1</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=5mkx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mkx OCA], [https://pdbe.org/5mkx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mkx RCSB], [https://www.ebi.ac.uk/pdbsum/5mkx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mkx ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/KAT2B_HUMAN KAT2B_HUMAN] Functions as a histone acetyltransferase (HAT) to promote transcriptional activation. Has significant histone acetyltransferase activity with core histones (H3 and H4), and also with nucleosome core particles. Also acetylates non-histone proteins, such as ACLY. Inhibits cell-cycle progression and counteracts the mitogenic activity of the adenoviral oncoprotein E1A. 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:8684459</ref> <ref>PMID:9707565</ref> <ref>PMID:10675335</ref> <ref>PMID:23932781</ref> 
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== 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>
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<div class="pdbe-citations 5mkx" style="background-color:#fffaf0;"></div>

==See Also==
*[[Histone acetyltransferase 3D structures|Histone acetyltransferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chung C-W]]