5cgp

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'''Unreleased structure'''
 
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The entry 5cgp is ON HOLD until Paper Publication
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==Selective pharmacological inhibition of the CREB binding protein bromodomain regulates inflammatory cytokines in macrophages and RGS4 in neurons==
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<StructureSection load='5cgp' size='340' side='right' caption='[[5cgp]], [[Resolution|resolution]] 1.96&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[5cgp]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CGP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CGP FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=53W:5-(3,5-DIMETHYL-1,2-OXAZOL-4-YL)-2-[2-(4-METHOXYPHENYL)ETHYL]-1-[2-(MORPHOLIN-4-YL)ETHYL]-1H-BENZIMIDAZOLE'>53W</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5cfw|5cfw]]</td></tr>
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<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>
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<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=5cgp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cgp OCA], [http://pdbe.org/5cgp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cgp RCSB], [http://www.ebi.ac.uk/pdbsum/5cgp PDBsum]</span></td></tr>
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</table>
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== Disease ==
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[[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>
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== Function ==
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[[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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Bromodomains are involved in transcriptional regulation through the recognition of acetyl lysine modifications on diverse proteins. Selective pharmacological modulators of bromodomains are lacking, although the largely hydrophobic nature of the pocket makes these modules attractive targets for small-molecule inhibitors. This work describes the structure-based design of a highly selective inhibitor of the CREB binding protein (CBP) bromodomain and its use in cell-based transcriptional profiling experiments. The inhibitor downregulated a number of inflammatory genes in macrophages that were not affected by a selective BET bromodomain inhibitor. In addition, the CBP bromodomain inhibitor modulated the mRNA level of the regulator of G-protein signaling 4 (RGS4) gene in neurons, suggesting a potential therapeutic opportunity for CBP inhibitors in the treatment of neurological disorders.
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Authors: Chekerl, E., Jones, L.
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Transcriptional Profiling of a Selective CREB Binding Protein Bromodomain Inhibitor Highlights Therapeutic Opportunities.,Chekler EL, Pellegrino JA, Lanz TA, Denny RA, Flick AC, Coe J, Langille J, Basak A, Liu S, Stock IA, Sahasrabudhe P, Bonin PD, Lee K, Pletcher MT, Jones LH Chem Biol. 2015 Dec 17;22(12):1588-96. doi: 10.1016/j.chembiol.2015.10.013. Epub , 2015 Dec 3. PMID:26670081<ref>PMID:26670081</ref>
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Description: Selective pharmacological inhibition of the CREB binding protein bromodomain regulates inflammatory cytokines in macrophages and RGS4 in neurons
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Jones, L]]
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<div class="pdbe-citations 5cgp" style="background-color:#fffaf0;"></div>
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[[Category: Chekerl, E]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Histone acetyltransferase]]
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[[Category: Chekler, E L]]
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[[Category: Jones, L H]]
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[[Category: Complex]]
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[[Category: Inhibitor]]
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[[Category: Transcription-inhibitor complex]]

Revision as of 18:41, 12 May 2016

Selective pharmacological inhibition of the CREB binding protein bromodomain regulates inflammatory cytokines in macrophages and RGS4 in neurons

5cgp, resolution 1.96Å

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