8qu3

NF-YB/C Heterodimer in Complex with a 13-mer NF-YA-derived Peptide Stabilized with C8-Hydrocarbon Linker

spinqualitylabelsall models 8qu3, resolution 1.41Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8qu3 is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.41Å Ligands: ACE, FMT, MK8, NH2, NLE, TRS Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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