7x4x: Difference between revisions
New page: '''Unreleased structure''' The entry 7x4x is ON HOLD Authors: Qu, L.Z. Description: BTB domain of KEAP1 in complex with MEF Category: Unreleased Structures Category: Qu, L.Z |
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==BTB domain of KEAP1 in complex with MEF== | |||
<StructureSection load='7x4x' size='340' side='right'caption='[[7x4x]], [[Resolution|resolution]] 2.96Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7x4x]] is a 6 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=7X4X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7X4X 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]] 2.96Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9J3:4-ethoxy-4-oxidanylidene-butanoic+acid'>9J3</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=7x4x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7x4x OCA], [https://pdbe.org/7x4x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7x4x RCSB], [https://www.ebi.ac.uk/pdbsum/7x4x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7x4x ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/KEAP1_HUMAN KEAP1_HUMAN] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Fumarates (fumaric acid esters), primarily dimethyl fumarate (DMF) and monoethyl fumarate (MEF) and its salts, are orally administered systemic agents used for the treatment of psoriasis and multiple sclerosis. It is widely believed that the pharmaceutical activities of fumarates are exerted through the Keap1-Nrf2 pathway. Although it has been revealed that DMF and MEF differentially modify specific Keap1 cysteine residues and result in the differential activation of Nrf2, how the modification of DMF and MEF impacts the biochemical properties of Keap1 has not been well characterized. Here, we found that both DMF and MEF can only modify the BTB domain of Keap1 and that only C151 is accessible for covalent binding in vitro. Dynamic fluorescence scanning (DSF) assays showed that the modification of DMF to Keap1 BTB increased its thermal stability, while the modification of MEF dramatically decreased its thermal stability. Further crystal structures revealed no significant conformational variation between the DMF-modified and MEF-modified BTBs. Overall, our biochemical and structural study provides a better understanding of the covalent modification of fumarates to Keap1 and may suggest fundamentally different mechanisms adopted by fumarates in regulating the Keap1-Nrf2 pathway. | |||
Characterization of the modification of Kelch-like ECH-associated protein 1 by different fumarates.,Qu L, Guo M, Zhang H, Chen X, Wei H, Jiang L, Li J, Chen Z, Dai S, Chen Y Biochem Biophys Res Commun. 2022 May 21;605:9-15. doi: , 10.1016/j.bbrc.2022.03.059. Epub 2022 Mar 12. PMID:35306364<ref>PMID:35306364</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Qu | <div class="pdbe-citations 7x4x" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Kelch-like protein 3D structures|Kelch-like protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Qu LZ]] | |||
Latest revision as of 09:55, 21 November 2024
BTB domain of KEAP1 in complex with MEFBTB domain of KEAP1 in complex with MEF
Structural highlights
FunctionPublication Abstract from PubMedFumarates (fumaric acid esters), primarily dimethyl fumarate (DMF) and monoethyl fumarate (MEF) and its salts, are orally administered systemic agents used for the treatment of psoriasis and multiple sclerosis. It is widely believed that the pharmaceutical activities of fumarates are exerted through the Keap1-Nrf2 pathway. Although it has been revealed that DMF and MEF differentially modify specific Keap1 cysteine residues and result in the differential activation of Nrf2, how the modification of DMF and MEF impacts the biochemical properties of Keap1 has not been well characterized. Here, we found that both DMF and MEF can only modify the BTB domain of Keap1 and that only C151 is accessible for covalent binding in vitro. Dynamic fluorescence scanning (DSF) assays showed that the modification of DMF to Keap1 BTB increased its thermal stability, while the modification of MEF dramatically decreased its thermal stability. Further crystal structures revealed no significant conformational variation between the DMF-modified and MEF-modified BTBs. Overall, our biochemical and structural study provides a better understanding of the covalent modification of fumarates to Keap1 and may suggest fundamentally different mechanisms adopted by fumarates in regulating the Keap1-Nrf2 pathway. Characterization of the modification of Kelch-like ECH-associated protein 1 by different fumarates.,Qu L, Guo M, Zhang H, Chen X, Wei H, Jiang L, Li J, Chen Z, Dai S, Chen Y Biochem Biophys Res Commun. 2022 May 21;605:9-15. doi: , 10.1016/j.bbrc.2022.03.059. Epub 2022 Mar 12. PMID:35306364[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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