000872856 001__ 872856
000872856 005__ 20210130004317.0
000872856 0247_ $$2doi$$a10.1111/febs.14736
000872856 0247_ $$2ISSN$$a0014-2956
000872856 0247_ $$2ISSN$$a0945-5795
000872856 0247_ $$2ISSN$$a1432-1033
000872856 0247_ $$2ISSN$$a1742-464X
000872856 0247_ $$2ISSN$$a1742-4658
000872856 0247_ $$2pmid$$apmid:30565859
000872856 0247_ $$2WOS$$aWOS:000467253400005
000872856 037__ $$aFZJ-2020-00324
000872856 041__ $$aEnglish
000872856 082__ $$a610
000872856 1001_ $$0P:(DE-HGF)0$$aYokoyama, Takeshi$$b0$$eCorresponding author
000872856 245__ $$aStructural and thermodynamic characterization of the binding of isoliquiritigenin to the first bromodomain of BRD4
000872856 260__ $$aOxford [u.a.]$$bWiley-Blackwell$$c2019
000872856 3367_ $$2DRIVER$$aarticle
000872856 3367_ $$2DataCite$$aOutput Types/Journal article
000872856 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1581406760_29861
000872856 3367_ $$2BibTeX$$aARTICLE
000872856 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000872856 3367_ $$00$$2EndNote$$aJournal Article
000872856 520__ $$aBromodomain-containing protein 4 (BRD4) recognizes the acetylated lysineof histone H4 via its bromodomains, leading to the recruitment of positivetranscription elongation factor b. Small molecules that inhibit BRD4 havepotential as anticancer agents by leading to the downregulation of specificoncogenes. Using X-ray crystallographic screening, we identified the BRD4inhibitory activity of isoliquiritigenin (ISL), a natural chalcone found inlicorice. Structural analysis revealed that ISL bound to BRD4 with a novelbinding mode and squeezed out one of the six conserved water moleculesthat form a strong hydrogen bond network. The thermodynamic analysisrevealed that the binding of ISL is enthalpy driven, suggesting that stronghydrogen bonds would compensate for the desolvation penalty. Neutronprotein crystallography further suggested that the favorable bindingenthalpy originates from the stabilization and optimization of the hydrogenbond network of the conserved water molecules. Here, we describe the noveltyand potential of ISL as a template for new BRD4 inhibitors.
000872856 536__ $$0G:(DE-HGF)POF3-6G4$$a6G4 - Jülich Centre for Neutron Research (JCNS) (POF3-623)$$cPOF3-623$$fPOF III$$x0
000872856 536__ $$0G:(DE-HGF)POF3-6G15$$a6G15 - FRM II / MLZ (POF3-6G15)$$cPOF3-6G15$$fPOF III$$x1
000872856 536__ $$0G:(DE-HGF)POF3-6215$$a6215 - Soft Matter, Health and Life Sciences (POF3-621)$$cPOF3-621$$fPOF III$$x2
000872856 588__ $$aDataset connected to CrossRef
000872856 65027 $$0V:(DE-MLZ)SciArea-160$$2V:(DE-HGF)$$aBiology$$x0
000872856 65017 $$0V:(DE-MLZ)GC-130-2016$$2V:(DE-HGF)$$aHealth and Life$$x0
000872856 693__ $$0EXP:(DE-MLZ)BIODIFF-20140101$$1EXP:(DE-MLZ)FRMII-20140101$$5EXP:(DE-MLZ)BIODIFF-20140101$$6EXP:(DE-MLZ)NL1-20140101$$aForschungs-Neutronenquelle Heinz Maier-Leibnitz $$eBIODIFF: Diffractometer for large unit cells$$fNL1$$x0
000872856 7001_ $$0P:(DE-HGF)0$$aMatsumoto, Kazunori$$b1
000872856 7001_ $$0P:(DE-HGF)0$$aOstermann, Andreas$$b2
000872856 7001_ $$0P:(DE-Juel1)138266$$aSchrader, Tobias E.$$b3$$ufzj
000872856 7001_ $$0P:(DE-HGF)0$$aNabeshima, Yuko$$b4
000872856 7001_ $$0P:(DE-HGF)0$$aMizuguchi, Mineyuki$$b5
000872856 773__ $$0PERI:(DE-600)2172518-4$$a10.1111/febs.14736$$gVol. 286, no. 9, p. 1656 - 1667$$n9$$p1656 - 1667$$tThe FEBS journal$$v286$$x1742-4658$$y2019
000872856 8564_ $$uhttps://juser.fz-juelich.de/record/872856/files/Yokoyama_et_al-2019-The_FEBS_Journal-1.pdf$$yRestricted
000872856 8564_ $$uhttps://juser.fz-juelich.de/record/872856/files/Yokoyama_et_al-2019-The_FEBS_Journal-1.pdf?subformat=pdfa$$xpdfa$$yRestricted
000872856 909CO $$ooai:juser.fz-juelich.de:872856$$pVDB$$pVDB:MLZ
000872856 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)138266$$aForschungszentrum Jülich$$b3$$kFZJ
000872856 9131_ $$0G:(DE-HGF)POF3-623$$1G:(DE-HGF)POF3-620$$2G:(DE-HGF)POF3-600$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$9G:(DE-HGF)POF3-6G4$$aDE-HGF$$bForschungsbereich Materie$$lVon Materie zu Materialien und Leben$$vFacility topic: Neutrons for Research on Condensed Matter$$x0
000872856 9131_ $$0G:(DE-HGF)POF3-6G15$$1G:(DE-HGF)POF3-6G0$$2G:(DE-HGF)POF3-600$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$9G:(DE-HGF)POF3-6G15$$aDE-HGF$$bForschungsbereich Materie$$lGroßgeräte: Materie$$vFRM II / MLZ$$x1
000872856 9131_ $$0G:(DE-HGF)POF3-621$$1G:(DE-HGF)POF3-620$$2G:(DE-HGF)POF3-600$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$9G:(DE-HGF)POF3-6215$$aDE-HGF$$bForschungsbereich Materie$$lVon Materie zu Materialien und Leben$$vIn-house research on the structure, dynamics and function of matter$$x2
000872856 9141_ $$y2019
000872856 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bFEBS J : 2017
000872856 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000872856 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000872856 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000872856 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search
000872856 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC
000872856 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List
000872856 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index
000872856 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000872856 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000872856 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences
000872856 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews
000872856 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5
000872856 920__ $$lyes
000872856 9201_ $$0I:(DE-Juel1)JCNS-FRM-II-20110218$$kJCNS-FRM-II$$lJCNS-FRM-II$$x0
000872856 9201_ $$0I:(DE-Juel1)JCNS-1-20110106$$kJCNS-1$$lNeutronenstreuung$$x1
000872856 9201_ $$0I:(DE-588b)4597118-3$$kMLZ$$lHeinz Maier-Leibnitz Zentrum$$x2
000872856 980__ $$ajournal
000872856 980__ $$aVDB
000872856 980__ $$aI:(DE-Juel1)JCNS-FRM-II-20110218
000872856 980__ $$aI:(DE-Juel1)JCNS-1-20110106
000872856 980__ $$aI:(DE-588b)4597118-3
000872856 980__ $$aUNRESTRICTED