7v2j: Difference between revisions

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-'''Unreleased structure'''
-The entry 7v2j is ON HOLD
+==Crystal Structure of the first bromodomain of human BRD4 in complex with the inhibitor 33==
+<StructureSection load='7v2j' size='340' side='right'caption='[[7v2j]], [[Resolution|resolution]] 2.24&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[7v2j]] 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=7V2J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7V2J FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.24&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5FZ:~{N}-(3-ethyl-6-methoxy-1,2-benzoxazol-5-yl)-4-methoxy-benzenesulfonamide'>5FZ</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7v2j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7v2j OCA], [https://pdbe.org/7v2j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7v2j RCSB], [https://www.ebi.ac.uk/pdbsum/7v2j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7v2j ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN] Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.<ref>PMID:12543779</ref> <ref>PMID:11733348</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+BRD4 plays a key role in the regulation of gene transcription and has been identified as an attractive target for cancer treatment. In this study, we designed 26 new compounds by modifying 3-ethyl-benzo[d]isoxazole core with sulfonamides. Most compounds exhibited potent BRD4 binding activities with DeltaT(m) values exceeding 6 degrees C. Two crystal structures of 11h and 11r in complex with BRD4(1) were obtained to characterize the binding patterns. Compounds 11h and 11r were effective for BRD4(1) binding and showed remarkable anti-proliferative activity against MV4-11 cells with IC(50) values of 0.78 and 0.87 muM. Furthermore, 11r (0.5-10 muM) concentration-dependently inhibited the expression levels of oncogenes including c-Myc and CDK6 in MV4-11 cells. Moreover, 11r (0.5-10 muM) concentration-dependently blocked cell cycle in MV4-11 cells at G(0)/G(1) phase and induced cell apoptosis. Compound 11r may serve as a new lead compound for further drug development.
-Authors: zhang, M., Wang, C., Zhang, C., Zhang, Y., Xu, Y.
+Design, synthesis and pharmacological characterization of N-(3-ethylbenzo[d]isoxazol-5-yl) sulfonamide derivatives as BRD4 inhibitors against acute myeloid leukemia.,Zhang MF, Luo XY, Zhang C, Wang C, Wu XS, Xiang QP, Xu Y, Zhang Y Acta Pharmacol Sin. 2022 Oct;43(10):2735-2748. doi: 10.1038/s41401-022-00881-y. , Epub 2022 Mar 9. PMID:35264812<ref>PMID:35264812</ref>
-Description: Crystal Structure of the first bromodomain of human BRD4 in complex with the inhibitor 33
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Zhang, Y]]
+<div class="pdbe-citations 7v2j" style="background-color:#fffaf0;"></div>
-[[Category: Zhang, M]]
-[[Category: Wang, C]]
+==See Also==
-[[Category: Zhang, C]]
+*[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]]
-[[Category: Xu, Y]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Wang C]]
+[[Category: Xu Y]]
+[[Category: Zhang C]]
+[[Category: Zhang M]]
+[[Category: Zhang Y]]