9juy

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'''Unreleased structure'''
 
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The entry 9juy is ON HOLD until Paper Publication
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==X-ray crystal structure of Y16513 in CBP==
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<StructureSection load='9juy' size='340' side='right'caption='[[9juy]], [[Resolution|resolution]] 1.42&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[9juy]] is a 1 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=9JUY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9JUY 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]] 1.42&#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=A1EDO:(5~{S})-1-(3-chloranyl-4-methoxy-phenyl)-5-[4-(3-methyl-1,2-benzoxazol-5-yl)-1-[(2~{S})-2-morpholin-4-ylpropyl]imidazol-2-yl]pyrrolidin-2-one'>A1EDO</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene></td></tr>
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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=9juy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9juy OCA], [https://pdbe.org/9juy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9juy RCSB], [https://www.ebi.ac.uk/pdbsum/9juy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9juy 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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Inhibition of the bromodomain of the cAMP response element binding protein (CREB)-binding protein (CBP) and its homologue p300 is an attractive therapeutic approach in oncology, particularly in acute myeloid leukemia (AML). In this study we describe the design, optimization, and evaluation of 5-imidazole-3-methylbenz[d]isoxazoles as novel, potent and selective CBP/p300 bromodomain inhibitors. Two of the representative compounds, 16t (Y16524) and 16u (Y16526), bound to the p300 bromodomain with IC(50) values of 0.01 and 0.03 muM, respectively. Furthermore, 16t and 16u potently inhibited the growth of AML cell lines, particularly MV4;11 cells with IC(50) values of 0.49 and 0.26 muM, respectively. The potent CBP/p300 bromodomain inhibitors represent a new class of compounds for the development of potential therapeutics against AML.
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Authors: Hu, J., Zhang, C., Luo, G., Tang, X., Wu, T., Shen, H., Zhao, X., Wu, X., Smaill, J., Zhang, Y., Xu, Y., Xiang, Q.
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Discovery of 5-imidazole-3-methylbenz[d]isoxazole derivatives as potent and selective CBP/p300 bromodomain inhibitors for the treatment of acute myeloid leukemia.,Hu JK, Tang X, Luo GL, Zhang C, Wu TB, Wang C, Shen H, Zhao XF, Wu XS, Smaill JB, Xu Y, Zhang Y, Xiang QP Acta Pharmacol Sin. 2025 Jan 31. doi: 10.1038/s41401-025-01478-x. PMID:39890943<ref>PMID:39890943</ref>
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Description: X-ray crystal structure of Y16513 in CBP
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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: Zhang, Y]]
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<div class="pdbe-citations 9juy" style="background-color:#fffaf0;"></div>
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[[Category: Shen, H]]
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== References ==
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[[Category: Zhang, C]]
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<references/>
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[[Category: Smaill, J]]
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__TOC__
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[[Category: Wu, X]]
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</StructureSection>
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[[Category: Xiang, Q]]
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[[Category: Homo sapiens]]
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[[Category: Hu, J]]
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[[Category: Large Structures]]
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[[Category: Wu, T]]
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[[Category: Hu J]]
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[[Category: Xu, Y]]
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[[Category: Luo G]]
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[[Category: Zhao, X]]
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[[Category: Shen H]]
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[[Category: Tang, X]]
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[[Category: Smaill J]]
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[[Category: Luo, G]]
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[[Category: Tang X]]
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[[Category: Wu T]]
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[[Category: Wu X]]
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[[Category: Xiang Q]]
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[[Category: Xu Y]]
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[[Category: Zhang C]]
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[[Category: Zhang Y]]
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[[Category: Zhao X]]

Revision as of 10:39, 12 March 2025

X-ray crystal structure of Y16513 in CBP

PDB ID 9juy

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