View source for 8qu4


==NF-YB/C Heterodimer in Complex with a 13-mer NF-YA-derived Peptide Stabilized with C8-Hydrocarbon Linker in an alternative binding pose==
<StructureSection load='8qu4' size='340' side='right'caption='[[8qu4]], [[Resolution|resolution]] 1.38&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8qu4]] 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=8QU4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8QU4 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]] 1.38&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MK8:2-METHYL-L-NORLEUCINE'>MK8</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=NLE:NORLEUCINE'>NLE</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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=8qu4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8qu4 OCA], [https://pdbe.org/8qu4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8qu4 RCSB], [https://www.ebi.ac.uk/pdbsum/8qu4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8qu4 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NFYA_HUMAN NFYA_HUMAN] Component of the sequence-specific heterotrimeric transcription factor (NF-Y) which specifically recognizes a 5'-CCAAT-3' box motif found in the promoters of its target genes. NF-Y can function as both an activator and a repressor, depending on its interacting cofactors. NF-YA positively regulates the transcription of the core clock component ARNTL/BMAL1.<ref>PMID:12741956</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Transcription factors (TFs) play a central role in gene regulation, and their malfunction can result in a plethora of severe diseases. TFs are therefore interesting therapeutic targets, but their involvement in protein-protein interaction networks and the frequent lack of well-defined binding pockets render them challenging targets for classical small molecules. As an alternative, peptide-based scaffolds have proven useful, in particular with an alpha-helical active conformation. Peptide-based strategies often require extensive structural optimization efforts, which could benefit from a more detailed understanding of the dynamics in inhibitor/protein interactions. In this study, we investigate how truncated stapled alpha-helical peptides interact with the transcription factor Nuclear Factor-Y (NF-Y). We identified a 13-mer minimal binding core region, for which two crystal structures with an altered C-terminal peptide conformation when bound to NF-Y were obtained. Subsequent molecular dynamics simulations confirmed that the C-terminal part of the stapled peptide is indeed relatively flexible while still showing defined interactions with NF-Y. Our findings highlight the importance of flexibility in the bound state of peptides, which can contribute to overall binding affinity.

Binding Dynamics of a Stapled Peptide Targeting the Transcription Factor NF-Y.,Durukan C, Arbore F, Klintrot R, Bigiotti C, Ilie IM, Vreede J, Grossmann TN, Hennig S Chembiochem. 2024 May 2;25(9):e202400020. doi: 10.1002/cbic.202400020. Epub 2024 , Apr 2. PMID:38470946<ref>PMID:38470946</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8qu4" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Arbore F]]
[[Category: Durukan C]]
[[Category: Grossmann TN]]
[[Category: Hennig S]]
[[Category: Klintrot CIR]]