2flu

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(New page: 200px<br /> <applet load="2flu" size="450" color="white" frame="true" align="right" spinBox="true" caption="2flu, resolution 1.50&Aring;" /> '''Crystal Structure o...)
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[[Image:2flu.gif|left|200px]]<br />
 
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<applet load="2flu" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2flu, resolution 1.50&Aring;" />
 
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'''Crystal Structure of the Kelch-Neh2 Complex'''<br />
 
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==Overview==
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==Crystal Structure of the Kelch-Neh2 Complex==
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Keap1 is a BTB-Kelch substrate adaptor protein that regulates steady-state, levels of Nrf2, a bZIP transcription factor, in response to oxidative, stress. We have determined the structure of the Kelch domain of Keap1, bound to a 16-mer peptide from Nrf2 containing a highly conserved DxETGE, motif. The Nrf2 peptide contains two short antiparallel beta-strands, connected by two overlapping type I beta-turns stabilized by the aspartate, and threonine residues. The beta-turn region fits into a binding pocket on, the top face of the Kelch domain and the glutamate residues form multiple, hydrogen bonds with highly conserved residues in Keap1. Mutagenesis, experiments confirmed the role of individual amino acids for binding of, Nrf2 to Keap1 and for Keap1-mediated repression of Nrf2-dependent gene, expression. Our results provide a detailed picture of how a BTB-Kelch, substrate adaptor protein binds to its cognate substrate and will enable, the rational design of novel chemopreventive agents.
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<StructureSection load='2flu' size='340' side='right'caption='[[2flu]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2flu]] is a 2 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=2FLU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FLU FirstGlance]. <br>
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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]] 1.5&#8491;</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=2flu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2flu OCA], [https://pdbe.org/2flu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2flu RCSB], [https://www.ebi.ac.uk/pdbsum/2flu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2flu ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/KEAP1_HUMAN KEAP1_HUMAN]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fl/2flu_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2flu ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Keap1 is a BTB-Kelch substrate adaptor protein that regulates steady-state levels of Nrf2, a bZIP transcription factor, in response to oxidative stress. We have determined the structure of the Kelch domain of Keap1 bound to a 16-mer peptide from Nrf2 containing a highly conserved DxETGE motif. The Nrf2 peptide contains two short antiparallel beta-strands connected by two overlapping type I beta-turns stabilized by the aspartate and threonine residues. The beta-turn region fits into a binding pocket on the top face of the Kelch domain and the glutamate residues form multiple hydrogen bonds with highly conserved residues in Keap1. Mutagenesis experiments confirmed the role of individual amino acids for binding of Nrf2 to Keap1 and for Keap1-mediated repression of Nrf2-dependent gene expression. Our results provide a detailed picture of how a BTB-Kelch substrate adaptor protein binds to its cognate substrate and will enable the rational design of novel chemopreventive agents.
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==About this Structure==
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Structure of the Keap1:Nrf2 interface provides mechanistic insight into Nrf2 signaling.,Lo SC, Li X, Henzl MT, Beamer LJ, Hannink M EMBO J. 2006 Aug 9;25(15):3605-17. Epub 2006 Aug 3. PMID:16888629<ref>PMID:16888629</ref>
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2FLU is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2FLU OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Structure of the Keap1:Nrf2 interface provides mechanistic insight into Nrf2 signaling., Lo SC, Li X, Henzl MT, Beamer LJ, Hannink M, EMBO J. 2006 Aug 9;25(15):3605-17. Epub 2006 Aug 3. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16888629 16888629]
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</div>
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[[Category: Homo sapiens]]
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<div class="pdbe-citations 2flu" style="background-color:#fffaf0;"></div>
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[[Category: Protein complex]]
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[[Category: Beamer, L.]]
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[[Category: Hannink, M.]]
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[[Category: Li, X.]]
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[[Category: Lo, J.]]
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[[Category: beta-propeller]]
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[[Category: kelch domain]]
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[[Category: protein-peptide complex]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 22:07:19 2007''
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==See Also==
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*[[Kelch-like protein 3D structures|Kelch-like protein 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Beamer L]]
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[[Category: Hannink M]]
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[[Category: Li X]]
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[[Category: Lo J]]

Current revision

Crystal Structure of the Kelch-Neh2 Complex

PDB ID 2flu

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