6QMP
NF-YB/C Heterodimer in Complex with NF-YA Peptide
Summary for 6QMP
| Entry DOI | 10.2210/pdb6qmp/pdb |
| Descriptor | Nuclear transcription factor Y subunit alpha, Nuclear transcription factor Y subunit beta, Nuclear transcription factor Y subunit gamma, ... (4 entities in total) |
| Functional Keywords | peptide histone fold transcription factor, transcription |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 3 |
| Total formula weight | 25657.87 |
| Authors | Kiehstaller, S.,Jeganathan, S.,Pearce, N.M.,Wendt, M.,Grossmann, T.N.,Hennig, S. (deposition date: 2019-02-08, release date: 2019-10-02, Last modification date: 2024-01-24) |
| Primary citation | Jeganathan, S.,Wendt, M.,Kiehstaller, S.,Brancaccio, D.,Kuepper, A.,Pospiech, N.,Carotenuto, A.,Novellino, E.,Hennig, S.,Grossmann, T.N. Constrained Peptides with Fine-Tuned Flexibility Inhibit NF-Y Transcription Factor Assembly. Angew.Chem.Int.Ed.Engl., 58:17351-17358, 2019 Cited by PubMed Abstract: Protein complex formation depends on the interplay between preorganization and flexibility of the binding epitopes involved. The design of epitope mimetics typically focuses on stabilizing a particular bioactive conformation, often without considering conformational dynamics, which limits the potential of peptidomimetics against challenging targets such as transcription factors. We developed a peptide-derived inhibitor of the NF-Y transcription factor by first constraining the conformation of an epitope through hydrocarbon stapling and then fine-tuning its flexibility. In the initial set of constrained peptides, a single non-interacting α-methyl group was observed to have a detrimental effect on complex stability. Biophysical characterization revealed how this methyl group affects the conformation of the peptide in its bound state. Adaption of the methylation pattern resulted in a peptide that inhibits transcription factor assembly and subsequent recruitment to the target DNA. PubMed: 31539186DOI: 10.1002/anie.201907901 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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