4xmb

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'''Unreleased structure'''
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==Crystal structure of 2,2'-(naphthalene-1,4-diylbis(((4-methoxyphenyl)sulfonyl)azanediyl))diacetamide bound to human Keap1 Kelch domain==
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<StructureSection load='4xmb' size='340' side='right' caption='[[4xmb]], [[Resolution|resolution]] 2.43&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4xmb]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XMB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XMB 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=41P:2,2-(NAPHTHALENE-1,4-DIYLBIS(((4-METHOXYPHENYL)SULFONYL)AZANEDIYL))DIACETAMIDE'>41P</scene></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=4xmb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xmb OCA], [http://pdbe.org/4xmb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xmb RCSB], [http://www.ebi.ac.uk/pdbsum/4xmb PDBsum]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Activation of the transcription factor Nrf2 has been posited to be a promising therapeutic strategy in a number of inflammatory and oxidative stress diseases due to its regulation of detoxifying enzymes. In this work, we have developed a comprehensive structure-activity relationship around a known, naphthalene-based non-electrophilic activator of Nrf2, and we report highly potent non-electrophilic activators of Nrf2. Computational docking analysis of a subset of the compound series demonstrates the importance of water molecule displacement for affinity, and the X-ray structure of di-amide 12e supports the computational analysis. One of the best compounds, acid 16b, has an IC50 of 61 nM in a fluorescence anisotropy assay and a Kd of 120 nM in a surface plasmon resonance assay. Additionally, we demonstrate that the ethyl ester of 16b is an efficacious inducer of Nrf2 target genes, exhibiting ex vivo efficacy similar to the well-known electrophilic activator, sulforaphane.
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The entry 4xmb is ON HOLD until Paper Publication
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Probing the structural requirements of non-electrophilic naphthalene-based Nrf2 activators.,Jain AD, Potteti H, Richardson BG, Kingsley L, Luciano JP, Ryuzoji AF, Lee H, Krunic A, Mesecar AD, Reddy SP, Moore TW Eur J Med Chem. 2015 Sep 4;103:252-268. doi: 10.1016/j.ejmech.2015.08.049. PMID:26363505<ref>PMID:26363505</ref>
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Authors: Luciano, J.P., Ryuzoji, A.F., Mesecar, A.D.
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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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Description:
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<div class="pdbe-citations 4xmb" style="background-color:#fffaf0;"></div>
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[[Category: Unreleased Structures]]
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== References ==
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[[Category: Ryuzoji, A.F]]
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<references/>
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[[Category: Mesecar, A.D]]
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__TOC__
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[[Category: Luciano, J.P]]
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</StructureSection>
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[[Category: Luciano, J P]]
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[[Category: Mesecar, A D]]
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[[Category: Ryuzoji, A F]]
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[[Category: Btb]]
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[[Category: Cul3]]
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[[Category: Cullin3]]
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[[Category: Nrf2 activator]]
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[[Category: Protein binding]]

Revision as of 14:37, 30 September 2015

Crystal structure of 2,2'-(naphthalene-1,4-diylbis(((4-methoxyphenyl)sulfonyl)azanediyl))diacetamide bound to human Keap1 Kelch domain

4xmb, resolution 2.43Å

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OCA

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