6ajv

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Current revision (10:32, 27 March 2024) (edit) (undo)
 
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<StructureSection load='6ajv' size='340' side='right'caption='[[6ajv]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
<StructureSection load='6ajv' size='340' side='right'caption='[[6ajv]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6ajv]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AJV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AJV FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6ajv]] 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=6AJV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AJV 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=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=HCC:2,4,4-TRIHYDROXYCHALCONE'>HCC</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
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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]] 1.45&#8491;</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=6ajv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ajv OCA], [http://pdbe.org/6ajv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ajv RCSB], [http://www.ebi.ac.uk/pdbsum/6ajv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ajv ProSAT]</span></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=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=HCC:2,4,4-TRIHYDROXYCHALCONE'>HCC</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=6ajv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ajv OCA], [https://pdbe.org/6ajv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ajv RCSB], [https://www.ebi.ac.uk/pdbsum/6ajv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ajv ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
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[[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>
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[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 ==
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[[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).
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[https://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Bromodomain-containing protein 4 (BRD4) recognizes the acetylated lysine of histone H4 via its bromodomains, leading to the recruitment of positive transcription elongation factor b. Small molecules that inhibit BRD4 have potential as anticancer agents by leading to the downregulation of specific oncogenes. Using X-ray crystallographic screening, we identified the BRD4 inhibitory activity of isoliquiritigenin (ISL), a natural chalcone found in licorice. Structural analysis revealed that ISL bound to BRD4 with a novel binding mode and squeezed out one of the six conserved water molecules that form a strong hydrogen bond network. The thermodynamic analysis revealed that the binding of ISL is enthalpy driven, suggesting that strong hydrogen bonds would compensate for the desolvation penalty. Neutron protein crystallography further suggested that the favorable binding enthalpy originates from the stabilization and optimization of the hydrogen bond network of the conserved water molecules. Here, we describe the novelty and potential of ISL as a template for new BRD4 inhibitors.
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Structural and thermodynamic characterization of the binding of isoliquiritigenin to the first bromodomain of BRD4.,Yokoyama T, Matsumoto K, Ostermann A, Schrader TE, Nabeshima Y, Mizuguchi M FEBS J. 2019 May;286(9):1656-1667. doi: 10.1111/febs.14736. Epub 2019 Jan 10. PMID:30565859<ref>PMID:30565859</ref>
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==See Also==
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*[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]]
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6ajv" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Matsumoto, K]]
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[[Category: Matsumoto K]]
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[[Category: Mizuguchi, M]]
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[[Category: Mizuguchi M]]
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[[Category: Nabeshima, Y]]
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[[Category: Nabeshima Y]]
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[[Category: Yokoyama, T]]
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[[Category: Yokoyama T]]
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[[Category: Brd4]]
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[[Category: Bromodomain]]
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[[Category: Inhibitor]]
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[[Category: Isoliquiritigenin]]
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[[Category: Transcription]]
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Current revision

Crystal structure of BRD4 in complex with isoliquiritigenin and DMSO (Cocktail No. 3)

PDB ID 6ajv

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