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6uf0
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 6uf0 is ON HOLD until Paper Publication Authors: Lazzara, P.R., David, B.P., Ankireddy, A., Richardson, B.G., Dye, K., Ratia, K.M., Reddy, S.P., Moo...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of N-(4-((4-methoxy-N-(2,2,2-trifluoroethyl)phenyl)sulfonamido)isoquinolin-1-yl)-N-((4-methoxyphenyl)sulfonyl)glycine bound to human Keap1 Kelch domain== | |
| + | <StructureSection load='6uf0' size='340' side='right'caption='[[6uf0]], [[Resolution|resolution]] 1.96Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6uf0]] 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=6UF0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UF0 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]] 1.96Å</td></tr> | ||
| + | <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=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=Q5V:N-[(4-methoxyphenyl)sulfonyl]-N-(4-{[(4-methoxyphenyl)sulfonyl](2,2,2-trifluoroethyl)amino}isoquinolin-1-yl)glycine'>Q5V</scene>, <scene name='pdbligand=Q5Y:N-[(4-methoxyphenyl)sulfonyl]-N-(4-{[(4-methoxyphenyl)sulfonyl]amino}naphthalen-1-yl)glycine'>Q5Y</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=6uf0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uf0 OCA], [https://pdbe.org/6uf0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uf0 RCSB], [https://www.ebi.ac.uk/pdbsum/6uf0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uf0 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/KEAP1_HUMAN KEAP1_HUMAN] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Pharmacological activation of NRF2 (nuclear factor erythroid 2-related factor 2) arises from blocking the interaction of NRF2 with its negative regulator, KEAP1 (Kelch-like ECH-associated protein 1). We previously reported an isoquinoline-based NRF2 activator, but this compound showed negative logD7.4 and a -2 charge at physiological pH, which may have limited its membrane permeability. In this work, we report potent, metabolically stable analogs that result from replacing a carboxymethyl group at the 4-position with a fluoroalkyl group. | ||
| - | + | Isoquinoline Kelch-like ECH-Associated Protein 1-Nuclear Factor (Erythroid-Derived 2)-like 2 (KEAP1-NRF2) Inhibitors with High Metabolic Stability.,Lazzara PR, David BP, Ankireddy A, Richardson BG, Dye K, Ratia KM, Reddy SP, Moore TW J Med Chem. 2019 Nov 14. doi: 10.1021/acs.jmedchem.9b01074. PMID:31682434<ref>PMID:31682434</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 6uf0" style="background-color:#fffaf0;"></div> |
| - | [[Category: David | + | |
| - | [[Category: | + | ==See Also== |
| - | [[Category: | + | *[[Kelch-like protein 3D structures|Kelch-like protein 3D structures]] |
| - | [[Category: | + | == References == |
| - | [[Category: | + | <references/> |
| - | [[Category: | + | __TOC__ |
| - | [[Category: | + | </StructureSection> |
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Ankireddy A]] | ||
| + | [[Category: David BP]] | ||
| + | [[Category: Dye K]] | ||
| + | [[Category: Lazzara PR]] | ||
| + | [[Category: Moore TW]] | ||
| + | [[Category: Ratia KM]] | ||
| + | [[Category: Reddy SP]] | ||
| + | [[Category: Richardson BG]] | ||
Current revision
Crystal structure of N-(4-((4-methoxy-N-(2,2,2-trifluoroethyl)phenyl)sulfonamido)isoquinolin-1-yl)-N-((4-methoxyphenyl)sulfonyl)glycine bound to human Keap1 Kelch domain
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Categories: Homo sapiens | Large Structures | Ankireddy A | David BP | Dye K | Lazzara PR | Moore TW | Ratia KM | Reddy SP | Richardson BG
