6fmp: Difference between revisions
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==Keap1 - peptide complex== | |||
<StructureSection load='6fmp' size='340' side='right' caption='[[6fmp]], [[Resolution|resolution]] 2.92Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6fmp]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FMP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FMP FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | |||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6fmp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fmp OCA], [http://pdbe.org/6fmp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fmp RCSB], [http://www.ebi.ac.uk/pdbsum/6fmp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fmp ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Noncovalent inhibitors of the Keap1-Nrf2 protein-protein interaction (PPI) have therapeutic potential in a range of disease states including neurodegenerative diseases (Parkinson's and Alzheimer's diseases), chronic obstructive pulmonary disease and various inflammatory conditions. By stalling Keap1-mediated ubiquitination of Nrf2, such compounds can enhance Nrf2 transcriptional activity and activate the expression of a range of genes with antioxidant response elements in their promoter regions. Keap1 inhibitors based on peptide and small-molecule templates have been identified. In this paper we develop the structure-activity relationships of the peptide series and identify a group of ligands incorporating unnatural amino acids that demonstrate improved binding affinity in fluorescence polarisation, differential scanning fluorimetry and isothermal titration calorimetry assays. These modified peptides have the potential for further development into peptidomimetic chemical probes to explore the role of Nrf2 in disease and as potential lead structures for drug development. | |||
Modified Peptide Inhibitors of the Keap1-Nrf2 Protein-Protein Interaction Incorporating Unnatural Amino Acids.,Georgakopoulos ND, Talapatra SK, Gatliff J, Kozielski F, Wells G Chembiochem. 2018 Jun 21. doi: 10.1002/cbic.201800170. PMID:29927029<ref>PMID:29927029</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6fmp" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Georgakopoulos, N D]] | |||
[[Category: Kozielski, F]] | |||
[[Category: Talapatra, S K]] | |||
[[Category: Wells, G]] | |||
[[Category: Inhibitor]] | |||
[[Category: Keap1]] | |||
[[Category: Kelch-domain]] | |||
[[Category: Neurodegenerative]] | |||
[[Category: Nrf2]] | |||
[[Category: Peptide binding protein]] | |||
Revision as of 00:53, 10 August 2018
Keap1 - peptide complexKeap1 - peptide complex
Structural highlights
Publication Abstract from PubMedNoncovalent inhibitors of the Keap1-Nrf2 protein-protein interaction (PPI) have therapeutic potential in a range of disease states including neurodegenerative diseases (Parkinson's and Alzheimer's diseases), chronic obstructive pulmonary disease and various inflammatory conditions. By stalling Keap1-mediated ubiquitination of Nrf2, such compounds can enhance Nrf2 transcriptional activity and activate the expression of a range of genes with antioxidant response elements in their promoter regions. Keap1 inhibitors based on peptide and small-molecule templates have been identified. In this paper we develop the structure-activity relationships of the peptide series and identify a group of ligands incorporating unnatural amino acids that demonstrate improved binding affinity in fluorescence polarisation, differential scanning fluorimetry and isothermal titration calorimetry assays. These modified peptides have the potential for further development into peptidomimetic chemical probes to explore the role of Nrf2 in disease and as potential lead structures for drug development. Modified Peptide Inhibitors of the Keap1-Nrf2 Protein-Protein Interaction Incorporating Unnatural Amino Acids.,Georgakopoulos ND, Talapatra SK, Gatliff J, Kozielski F, Wells G Chembiochem. 2018 Jun 21. doi: 10.1002/cbic.201800170. PMID:29927029[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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