View source for 6fqu


==Crystal structure of CREBBP bromodomain complexd with DR09==
<StructureSection load='6fqu' size='340' side='right' caption='[[6fqu]], [[Resolution|resolution]] 1.43&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6fqu]] is a 1 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=6FQU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FQU FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=E3B:1-[3-[3-[3,3-bis(fluoranyl)piperidin-1-yl]phenyl]-4-ethoxy-phenyl]ethanone'>E3B</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CREBBP, CBP ([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=6fqu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fqu OCA], [http://pdbe.org/6fqu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fqu RCSB], [http://www.ebi.ac.uk/pdbsum/6fqu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fqu ProSAT]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/CBP_HUMAN CBP_HUMAN]] Note=Chromosomal aberrations involving CREBBP may be a cause of acute myeloid leukemias. Translocation t(8;16)(p11;p13) with KAT6A; translocation t(11;16)(q23;p13.3) with MLL/HRX; translocation t(10;16)(q22;p13) with KAT6B. KAT6A-CREBBP may induce leukemia by inhibiting RUNX1-mediated transcription.  Defects in CREBBP are a cause of Rubinstein-Taybi syndrome type 1 (RSTS1) [MIM:[http://omim.org/entry/180849 180849]]. RSTS1 is an autosomal dominant disorder characterized by craniofacial abnormalities, broad thumbs, broad big toes, mental retardation and a propensity for development of malignancies.<ref>PMID:11331617</ref> <ref>PMID:12114483</ref> <ref>PMID:12566391</ref> <ref>PMID:15706485</ref>  
== Function ==
[[http://www.uniprot.org/uniprot/CBP_HUMAN CBP_HUMAN]] Acetylates histones, giving a specific tag for transcriptional activation. Also acetylates non-histone proteins, like NCOA3 and FOXO1. Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1 in the presence of EP300.<ref>PMID:9707565</ref> <ref>PMID:11154691</ref> <ref>PMID:12738767</ref> <ref>PMID:12929931</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
We analyze 20 crystal structures of complexes between the CBP bromodomain and small-molecule ligands that belong to eight different chemotypes identified by docking. The binding motif of the moiety that mimics the natural ligand (acetylated side chain of lysine) at the bottom of the binding pocket is conserved. In stark contrast, the rest of the ligands form different interactions with different side chains and backbone polar groups on the outer rim of the binding pocket. Hydrogen bonds are direct or water-bridged. van der Waals contacts are optimized by rotations of hydrophobic side chains and a slight inward displacement of the ZA loop. Rare types of interactions are observed for some of the ligands.

Binding Motifs in the CBP Bromodomain: An Analysis of 20 Crystal Structures of Complexes with Small Molecules.,Zhu J, Dong J, Batiste L, Unzue A, Dolbois A, Pascanu V, Sledz P, Nevado C, Caflisch A ACS Med Chem Lett. 2018 Aug 8;9(9):929-934. doi: 10.1021/acsmedchemlett.8b00286. , eCollection 2018 Sep 13. PMID:30258543<ref>PMID:30258543</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6fqu" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Histone acetyltransferase]]
[[Category: Human]]
[[Category: Caflisch, A]]
[[Category: Zhu, J]]
[[Category: Bromodomain]]
[[Category: Inhibitor]]
[[Category: Transferase]]