View source for 3zgc


==crystal structure of the KEAP1-NEH2 complex==
<StructureSection load='3zgc' size='340' side='right'caption='[[3zgc]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3zgc]] is a 3 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=3ZGC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZGC 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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</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=3zgc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zgc OCA], [https://pdbe.org/3zgc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zgc RCSB], [https://www.ebi.ac.uk/pdbsum/3zgc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zgc ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/KEAP1_HUMAN KEAP1_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Keap1 is a substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex and plays an important role in the cellular response to oxidative stress. It binds Nrf2 with its Kelch domain and thus triggers the ubiquitinylation and degradation of Nrf2. Oxidative stress prevents the degradation of Nrf2 and leads to the activation of cytoprotective genes. Therefore, Keap1 is an attractive drug target in inflammatory diseases. The support of a medicinal chemistry effort by structural research requires a robust crystallization system in which the crystals are preferably suited for performing soaking experiments. This facilitates the generation of protein-ligand complexes in a routine and high-throughput manner. The structure of human Keap1 has been described previously. In this crystal form, however, the binding site for Nrf2 was blocked by a crystal contact. This interaction was analysed and mutations were introduced to disrupt this crystal contact. One double mutation (E540A/E542A) crystallized in a new crystal form in which the binding site for Nrf2 was not blocked and was accessible to small-molecule ligands. The crystal structures of the apo form of the mutated Keap1 Kelch domain (1.98 A resolution) and of the complex with an Nrf2-derived peptide obtained by soaking (2.20 A resolution) are reported.

Crystal-contact engineering to obtain a crystal form of the Kelch domain of human Keap1 suitable for ligand-soaking experiments.,Horer S, Reinert D, Ostmann K, Hoevels Y, Nar H Acta Crystallogr Sect F Struct Biol Cryst Commun. 2013 Jun;69(Pt 6):592-6. doi:, 10.1107/S174430911301124X. Epub 2013 May 23. PMID:23722832<ref>PMID:23722832</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3zgc" 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: Hoerer S]]
[[Category: Hoevels Y]]
[[Category: Nar H]]
[[Category: Ostmann K]]
[[Category: Reinert D]]