5cpe: Difference between revisions

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 ==Crystal Structure of the first bromodomain of human BRD4 in complex with benzo[cd]indol-2(1H)-one ligand==
-<StructureSection load='5cpe' size='340' side='right' caption='[[5cpe]], [[Resolution|resolution]] 1.62&Aring;' scene=''>
+<StructureSection load='5cpe' size='340' side='right'caption='[[5cpe]], [[Resolution|resolution]] 1.62&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5cpe]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CPE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CPE FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5cpe]] 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=5CPE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CPE FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EB2:N-CYCLOHEPTYL-1-ETHYL-2-OXO-1,2-DIHYDROBENZO[CD]INDOLE-6-SULFONAMIDE'>EB2</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.62&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5c0i|5c0i]], [[5cp5|5cp5]], [[5cqt|5cqt]], [[5crm|5crm]], [[5crz|5crz]], [[5cs8|5cs8]], [[5ctl|5ctl]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EB2:N-CYCLOHEPTYL-1-ETHYL-2-OXO-1,2-DIHYDROBENZO[CD]INDOLE-6-SULFONAMIDE'>EB2</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></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=5cpe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cpe OCA], [http://pdbe.org/5cpe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cpe RCSB], [http://www.ebi.ac.uk/pdbsum/5cpe PDBsum]</span></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=5cpe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cpe OCA], [https://pdbe.org/5cpe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5cpe RCSB], [https://www.ebi.ac.uk/pdbsum/5cpe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5cpe ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://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>
+[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 ==
-[[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).
+[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 ==
-The discovery of inhibitors of bromodomain and extra terminal domain (BET) has achieved great progress, and at least seven inhibitors have progressed into clinical trials for the treatment of cancer or inflammatory diseases. Here, we describe the identification, optimization, and evaluation of benzo[cd]indol-2(1H)-one containing compounds as a new class of BET bromodomain inhibitors, starting from structure-based virtual screening (SBVS). Through structure-based optimization, potent compounds were obtained with significantly improved activity. The two most potent compounds bind to the BRD4 bromodomain, with Kd values of 124 and 137 nM. Selected compounds exhibited high selectivity over other non-BET subfamily members. Notably, compound 85 demonstrated a reasonable antiproliferation effect on MV4;11 leukemia cells and exhibited a good pharmacokinetic profile with high oral bioavailability (75.8%) and moderate half-life (T1/2 = 3.95 h). The resulting lead molecule 85 represents a new, potent, and selective class of BET bromodomain inhibitors for the development of therapeutics to treat cancer and inflammatory diseases.
-Discovery of Benzo[cd]indol-2(1H)-ones as Potent and Specific BET Bromodomain Inhibitors: Structure-Based Virtual Screening, Optimization, and Biological Evaluation.,Xue X, Zhang Y, Liu Z, Song M, Xing Y, Xiang Q, Wang Z, Tu Z, Zhou Y, Ding K, Xu Y J Med Chem. 2016 Jan 12. PMID:26731490<ref>PMID:26731490</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+==See Also==
-</div>
+*[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]]
-<div class="pdbe-citations 5cpe" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Liu, Z]]
+[[Category: Homo sapiens]]
-[[Category: Song, M]]
+[[Category: Large Structures]]
-[[Category: Xu, Y]]
+[[Category: Liu Z]]
-[[Category: Xue, X]]
+[[Category: Song M]]
-[[Category: Zhang, Y]]
+[[Category: Xu Y]]
-[[Category: Brd4]]
+[[Category: Xue X]]
-[[Category: Bromodomain]]
+[[Category: Zhang Y]]
-[[Category: Four alpha helice]]
-[[Category: Signaling protein-inhibitor complex]]
-[[Category: Transcription-transcr]]