6tg8: Difference between revisions
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==== | ==Crystal structure of the Kelch domain in complex with 11 amino acid peptide (model of the ETGE loop)== | ||
<StructureSection load='6tg8' size='340' side='right'caption='[[6tg8]]' scene=''> | <StructureSection load='6tg8' size='340' side='right'caption='[[6tg8]], [[Resolution|resolution]] 2.75Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[6tg8]] 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=6TG8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TG8 FirstGlance]. <br> | ||
</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=6tg8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tg8 OCA], [https://pdbe.org/6tg8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tg8 RCSB], [https://www.ebi.ac.uk/pdbsum/6tg8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tg8 ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.75Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</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=6tg8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tg8 OCA], [https://pdbe.org/6tg8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tg8 RCSB], [https://www.ebi.ac.uk/pdbsum/6tg8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tg8 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/KEAP1_HUMAN KEAP1_HUMAN] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
This work is about synergy of theory and experiment in revealing mechanism of binding of dipeptidyl peptidase III (DPP III) and Kelch-like ECH-associated protein 1 (KEAP1), the main cellular sensor of oxidative stress. The NRF2 KEAP1 signaling pathway is important for cell protection, but it is also impaired in many cancer cells where NRF2 target gene expression leads to resistance to chemotherapeutic drugs. DPP III competitively binds to KEAP1 in the conditions of oxidative stress and induces release of NRF2 and its translocation into nucleus. The binding is established mainly through the ETGE motif of DPP III and the Kelch domain of KEAP1. However, although part of a flexible loop, ETGE itself is firmly attached to the DPP III surface by strong hydrogen bonds. Using combined computational and experimental study, we found that DPP III Kelch binding is a two-step process comprising the endergonic loop detachment and exergonic DPP III Kelch interaction. Substitution of arginines, which keep the ETGE motif attached, decreases the work needed for its release and increases DPP III Kelch binding affinity. Interestingly, mutations of one of these arginine residues have been reported in cBioPortal for cancer genomics, implicating its possible involvement in cancer development. Communicated by Ramaswamy H. Sarma. | |||
Binding of dipeptidyl peptidase III to the oxidative stress cell sensor Kelch-like ECH-associated protein 1 is a two-step process.,Matic S, Kekez I, Tomin M, Bogar F, Supljika F, Kazazic S, Hanic M, Jha S, Brkic H, Bourgeois B, Madl T, Gruber K, Macheroux P, Matkovic-Calogovic D, Matovina M, Tomic S J Biomol Struct Dyn. 2020 Aug 18:1-12. doi: 10.1080/07391102.2020.1804455. PMID:32811353<ref>PMID:32811353</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6tg8" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Kelch-like protein 3D structures|Kelch-like protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Kekez I]] | ||
[[Category: Matic S]] | |||
[[Category: Matkovic-Calogovic D]] | |||
[[Category: Tomic S]] | |||