3p1c

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[[Image:3p1c.png|left|200px]]
 
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==Crystal structure of the bromodomain of human CREBBP in complex with acetylated lysine==
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The line below this paragraph, containing "STRUCTURE_3p1c", creates the "Structure Box" on the page.
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<StructureSection load='3p1c' size='340' side='right'caption='[[3p1c]], [[Resolution|resolution]] 1.82&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3p1c]] 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=3P1C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3P1C FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.82&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ALY:N(6)-ACETYLLYSINE'>ALY</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</scene></td></tr>
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{{STRUCTURE_3p1c| PDB=3p1c | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3p1c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p1c OCA], [https://pdbe.org/3p1c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3p1c RCSB], [https://www.ebi.ac.uk/pdbsum/3p1c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3p1c ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://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:[https://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>
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== Function ==
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[https://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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Bromodomains (BRDs) are protein interaction modules that specifically recognize epsilon-N-lysine acetylation motifs, a key event in the reading process of epigenetic marks. The 61 BRDs in the human genome cluster into eight families based on structure/sequence similarity. Here, we present 29 high-resolution crystal structures, covering all BRD families. Comprehensive crossfamily structural analysis identifies conserved and family-specific structural features that are necessary for specific acetylation-dependent substrate recognition. Screening of more than 30 representative BRDs against systematic histone-peptide arrays identifies new BRD substrates and reveals a strong influence of flanking posttranslational modifications, such as acetylation and phosphorylation, suggesting that BRDs recognize combinations of marks rather than singly acetylated sequences. We further uncovered a structural mechanism for the simultaneous binding and recognition of diverse diacetyl-containing peptides by BRD4. These data provide a foundation for structure-based drug design of specific inhibitors for this emerging target family.
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===Crystal structure of the bromodomain of human CREBBP in complex with acetylated lysine===
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Histone recognition and large-scale structural analysis of the human bromodomain family.,Filippakopoulos P, Picaud S, Mangos M, Keates T, Lambert JP, Barsyte-Lovejoy D, Felletar I, Volkmer R, Muller S, Pawson T, Gingras AC, Arrowsmith CH, Knapp S Cell. 2012 Mar 30;149(1):214-31. PMID:22464331<ref>PMID:22464331</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3p1c" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_22464331}}, adds the Publication Abstract to the page
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*[[CREB-binding protein|CREB-binding protein]]
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(as it appears on PubMed at http://www.pubmed.gov), where 22464331 is the PubMed ID number.
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*[[CREB-binding protein 3D structures|CREB-binding protein 3D structures]]
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== References ==
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{{ABSTRACT_PUBMED_22464331}}
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<references/>
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__TOC__
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==About this Structure==
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</StructureSection>
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[[3p1c]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P1C OCA].
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==Reference==
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<ref group="xtra">PMID:022464331</ref><references group="xtra"/>
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[[Category: Histone acetyltransferase]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Arrowsmith, C H.]]
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[[Category: Large Structures]]
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[[Category: Bountra, C.]]
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[[Category: Arrowsmith CH]]
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[[Category: Delft, F Von.]]
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[[Category: Bountra C]]
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[[Category: Edwards, A M.]]
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[[Category: Edwards AM]]
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[[Category: Fedorov, O.]]
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[[Category: Fedorov O]]
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[[Category: Feletar, I.]]
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[[Category: Feletar I]]
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[[Category: Filippakopoulos, P.]]
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[[Category: Filippakopoulos P]]
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[[Category: Knapp, S.]]
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[[Category: Knapp S]]
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[[Category: Muniz, J.]]
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[[Category: Muniz J]]
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[[Category: Picaud, S.]]
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[[Category: Picaud S]]
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[[Category: SGC, Structural Genomics Consortium.]]
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[[Category: Weigelt J]]
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[[Category: Weigelt, J.]]
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[[Category: Von Delft F]]
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[[Category: Bromodomain]]
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[[Category: Cbp]]
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[[Category: Creb binding protein isoform some]]
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[[Category: Crebbp]]
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[[Category: Kat3a]]
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[[Category: Rst]]
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[[Category: Rst]]
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[[Category: Sgc]]
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[[Category: Structural genomics consortium]]
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[[Category: Transcription]]
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Current revision

Crystal structure of the bromodomain of human CREBBP in complex with acetylated lysine

PDB ID 3p1c

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