7ko0: Difference between revisions
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<StructureSection load='7ko0' size='340' side='right'caption='[[7ko0]], [[Resolution|resolution]] 1.90Å' scene=''> | <StructureSection load='7ko0' size='340' side='right'caption='[[7ko0]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7ko0]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KO0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KO0 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7ko0]] 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=7KO0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KO0 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5W2:4-[[4-[[3-(~{TERT}-BUTYLSULFONYLAMINO)-4-CHLORANYL-PHENYL]AMINO]-5-METHYL-PYRIMIDIN-2-YL]AMINO]-2-FLUORANYL-~{N}-(1-METHYLPIPERIDIN-4-YL)BENZAMIDE'>5W2</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]] 1.9Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5W2:4-[[4-[[3-(~{TERT}-BUTYLSULFONYLAMINO)-4-CHLORANYL-PHENYL]AMINO]-5-METHYL-PYRIMIDIN-2-YL]AMINO]-2-FLUORANYL-~{N}-(1-METHYLPIPERIDIN-4-YL)BENZAMIDE'>5W2</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'>[https://proteopedia.org/fgij/fg.htm?mol=7ko0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ko0 OCA], [https://pdbe.org/7ko0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ko0 RCSB], [https://www.ebi.ac.uk/pdbsum/7ko0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ko0 ProSAT]</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=7ko0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ko0 OCA], [https://pdbe.org/7ko0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ko0 RCSB], [https://www.ebi.ac.uk/pdbsum/7ko0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ko0 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == 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 == | == 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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</div> | </div> | ||
<div class="pdbe-citations 7ko0" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 7ko0" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Karim | [[Category: Karim MR]] | ||
[[Category: Schonbrunn | [[Category: Schonbrunn E]] | ||
[[Category: Zhu | [[Category: Zhu JY]] | ||
Latest revision as of 18:28, 18 October 2023
Crystal structure of the second bromodomain (BD2) of human BRD4 bound to SG3-179Crystal structure of the second bromodomain (BD2) of human BRD4 bound to SG3-179
Structural highlights
DiseaseBRD4_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.[1] [2] FunctionBRD4_HUMAN Plays a role in a process governing chromosomal dynamics during mitosis (By similarity). Publication Abstract from PubMedBRD4 and other members of the bromodomain and extraterminal (BET) family of proteins are promising epigenetic targets for the development of novel therapeutics. Among the reported BRD4 inhibitors are dihydropteridinones and benzopyrimidodiazepinones originally designed to target the kinases PLK1, ERK5, and LRRK2. While these kinase inhibitors were identified as BRD4 inhibitors, little is known about their binding potential and structural details of interaction with the other BET bromodomains. We comprehensively characterized a series of known and newly identified dual BRD4-kinase inhibitors against all eight individual BET bromodomains. A detailed analysis of 23 novel cocrystal structures of BET-kinase inhibitor complexes in combination with direct binding assays and cell signaling studies revealed significant differences in molecular shape complementarity and inhibitory potential. Collectively, the data offer new insights into the action of kinase inhibitors across BET bromodomains, which may aid the development of drugs to inhibit certain BET proteins and kinases differentially. Differential BET Bromodomain Inhibition by Dihydropteridinone and Pyrimidodiazepinone Kinase Inhibitors.,Karim RM, Bikowitz MJ, Chan A, Zhu JY, Grassie D, Becker A, Berndt N, Gunawan S, Lawrence NJ, Schonbrunn E J Med Chem. 2021 Nov 11;64(21):15772-15786. doi: 10.1021/acs.jmedchem.1c01096., Epub 2021 Oct 28. PMID:34710325[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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