8QU2
NF-YB/C Heterodimer in Complex with a 16-mer NF-YA-derived Peptide Stabilized with C8-Hydrocarbon Linker
Summary for 8QU2
Entry DOI | 10.2210/pdb8qu2/pdb |
Related | 8QU3 |
Descriptor | Nuclear transcription factor Y subunit alpha, Nuclear transcription factor Y subunit beta, Nuclear transcription factor Y subunit gamma, ... (7 entities in total) |
Functional Keywords | peptidometic inhibitor, transcription |
Biological source | Homo sapiens (human) More |
Total number of polymer chains | 3 |
Total formula weight | 24534.60 |
Authors | Durukan, C.,Arbore, F.,Klintrot, C.I.R.,Grossmann, T.N.,Hennig, S. (deposition date: 2023-10-13, release date: 2024-03-20, Last modification date: 2024-11-13) |
Primary citation | Durukan, C.,Arbore, F.,Klintrot, R.,Bigiotti, C.,Ilie, I.M.,Vreede, J.,Grossmann, T.N.,Hennig, S. Binding Dynamics of a Stapled Peptide Targeting the Transcription Factor NF-Y. Chembiochem, 25:e202400020-e202400020, 2024 Cited by PubMed Abstract: 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 α-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 α-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. PubMed: 38470946DOI: 10.1002/cbic.202400020 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (1.45 Å) |
Structure validation
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