4cxi: Difference between revisions
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<StructureSection load='4cxi' size='340' side='right'caption='[[4cxi]], [[Resolution|resolution]] 2.35Å' scene=''> | <StructureSection load='4cxi' size='340' side='right'caption='[[4cxi]], [[Resolution|resolution]] 2.35Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4cxi]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4cxi]] 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=4CXI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CXI FirstGlance]. <br> | ||
</td></tr> | </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=4cxi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cxi OCA], [https://pdbe.org/4cxi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cxi RCSB], [https://www.ebi.ac.uk/pdbsum/4cxi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cxi ProSAT]</span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | |||
[[https://www.uniprot.org/uniprot/KEAP1_HUMAN KEAP1_HUMAN]] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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==See Also== | ==See Also== | ||
*[[Kelch-like protein|Kelch-like protein]] | *[[Kelch-like protein 3D structures|Kelch-like protein 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Callahan | [[Category: Callahan JF]] | ||
[[Category: Carr | [[Category: Carr R]] | ||
[[Category: Cleasby | [[Category: Cleasby A]] | ||
[[Category: Concha | [[Category: Concha N]] | ||
[[Category: Davies | [[Category: Davies TG]] | ||
[[Category: Day | [[Category: Day PJ]] | ||
[[Category: Kerns | [[Category: Kerns JK]] | ||
[[Category: Qi | [[Category: Qi H]] | ||
[[Category: Richardson | [[Category: Richardson C]] | ||
[[Category: Sweitzer | [[Category: Sweitzer T]] | ||
[[Category: Tickle | [[Category: Tickle IJ]] | ||
[[Category: Ward | [[Category: Ward P]] | ||
[[Category: Williams | [[Category: Williams PA]] | ||
[[Category: Yon | [[Category: Yon J]] | ||
Revision as of 10:37, 14 September 2022
BTB domain of KEAP1BTB domain of KEAP1
Structural highlights
FunctionPublication Abstract from PubMedThe protein Keap1 is central to the regulation of the Nrf2-mediated cytoprotective response, and is increasingly recognized as an important target for therapeutic intervention in a range of diseases involving excessive oxidative stress and inflammation. The BTB domain of Keap1 plays key roles in sensing environmental electrophiles and in mediating interactions with the Cul3/Rbx1 E3 ubiquitin ligase system, and is believed to be the target for several small molecule covalent activators of the Nrf2 pathway. However, despite structural information being available for several BTB domains from related proteins, there have been no reported crystal structures of Keap1 BTB, and this has precluded a detailed understanding of its mechanism of action and interaction with antagonists. We report here the first structure of the BTB domain of Keap1, which is thought to contain the key cysteine residue responsible for interaction with electrophiles, as well as structures of the covalent complex with the antagonist CDDO/bardoxolone, and of the constitutively inactive C151W BTB mutant. In addition to providing the first structural confirmation of antagonist binding to Keap1 BTB, we also present biochemical evidence that adduction of Cys 151 by CDDO is capable of inhibiting the binding of Cul3 to Keap1, and discuss how this class of compound might exert Nrf2 activation through disruption of the BTB-Cul3 interface. Structure of the BTB Domain of Keap1 and Its Interaction with the Triterpenoid Antagonist CDDO.,Cleasby A, Yon J, Day PJ, Richardson C, Tickle IJ, Williams PA, Callahan JF, Carr R, Concha N, Kerns JK, Qi H, Sweitzer T, Ward P, Davies TG PLoS One. 2014 Jun 4;9(6):e98896. doi: 10.1371/journal.pone.0098896. eCollection , 2014. PMID:24896564[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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