4xmb
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 4xmb is ON HOLD Authors: Luciano, J.P., Ryuzoji, A.F., Mesecar, A.D. Description: Category: Unreleased Structures Category: Ryuzoji, A.F [...) |
|||
| (5 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of 2,2'-(naphthalene-1,4-diylbis(((4-methoxyphenyl)sulfonyl)azanediyl))diacetamide bound to human Keap1 Kelch domain== | |
| + | <StructureSection load='4xmb' size='340' side='right'caption='[[4xmb]], [[Resolution|resolution]] 2.43Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4xmb]] 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=4XMB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XMB FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.428Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=41P:2,2-(NAPHTHALENE-1,4-DIYLBIS(((4-METHOXYPHENYL)SULFONYL)AZANEDIYL))DIACETAMIDE'>41P</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=4xmb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xmb OCA], [https://pdbe.org/4xmb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xmb RCSB], [https://www.ebi.ac.uk/pdbsum/4xmb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xmb ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/KEAP1_HUMAN KEAP1_HUMAN] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 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. | ||
| - | + | 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> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 4xmb" style="background-color:#fffaf0;"></div> |
| - | [[Category: Mesecar | + | |
| - | [[Category: | + | ==See Also== |
| + | *[[Kelch-like protein 3D structures|Kelch-like protein 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Luciano JP]] | ||
| + | [[Category: Mesecar AD]] | ||
| + | [[Category: Ryuzoji AF]] | ||
Current revision
Crystal structure of 2,2'-(naphthalene-1,4-diylbis(((4-methoxyphenyl)sulfonyl)azanediyl))diacetamide bound to human Keap1 Kelch domain
| |||||||||||
