View source for 5lvq


==Crystal structure of human PCAF bromodomain in complex with compound-D (CPD-D), N-methyl-2-(tetrahydro-2H-pyran-4-yloxy)benzamide==
<StructureSection load='5lvq' size='340' side='right'caption='[[5lvq]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5lvq]] 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=5LVQ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5LVQ FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2LX:N-METHYL-2-(TETRAHYDRO-2H-PYRAN-4-YLOXY)BENZAMIDE'>2LX</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</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">KAT2B, PCAF ([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://proteopedia.org/fgij/fg.htm?mol=5lvq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lvq OCA], [http://pdbe.org/5lvq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lvq RCSB], [http://www.ebi.ac.uk/pdbsum/5lvq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lvq ProSAT]</span></td></tr>
</table>
== Function ==
[[http://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>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The discovery of novel bromodomain inhibitors by fragment screening is complicated by the presence of dimethyl sulfoxide (DMSO), an acetyl-lysine mimetic, that can compromise the detection of low affinity fragments. We demonstrate surface plasmon resonance as a primary fragment screening approach for the discovery of novel bromodomain scaffolds, by describing a protocol to overcome the DMSO interference issue. We describe the discovery of several novel small molecules scaffolds that inhibit the bromodomains PCAF, BRD4, and CREBBP, representing canonical members of three out of the seven subfamilies of bromodomains. High-resolution crystal structures of the complexes of key fragments binding to BRD4(1), CREBBP, and PCAF were determined to provide binding mode data to aid the development of potent and selective inhibitors of PCAF, CREBBP, and BRD4.

Discovery of New Bromodomain Scaffolds by Biosensor Fragment Screening.,Navratilova I, Aristotelous T, Picaud S, Chaikuad A, Knapp S, Filappakopoulos P, Hopkins AL ACS Med Chem Lett. 2016 Sep 20;7(12):1213-1218. eCollection 2016 Dec 8. PMID:27994766<ref>PMID:27994766</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5lvq" style="background-color:#fffaf0;"></div>

==See Also==
*[[Histone acetyltransferase 3D structures|Histone acetyltransferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Histone acetyltransferase]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Arrowsmith, C H]]
[[Category: Bountra, C]]
[[Category: Chaikuad, A]]
[[Category: Delft, F von]]
[[Category: Edwards, A M]]
[[Category: Filippakopoulos, P]]
[[Category: Hopkins, A L]]
[[Category: Knapp, S]]
[[Category: Structural genomic]]
[[Category: Acetylation]]
[[Category: Acetyllysine]]
[[Category: Bromodomain]]
[[Category: Epigenetic]]
[[Category: Histone]]
[[Category: Histone acetyltransferase kat2b]]
[[Category: Signaling protein]]
[[Category: Transferase]]