6ZUF

Urea-based Foldamer Inhibitor chimera C2 in complex with ASF1 Histone chaperone

Summary for 6ZUF

• Entry DOI: 10.2210/pdb6zuf/pdb
• Descriptor: Histone chaperone ASF1A, C2 foldamer/peptide hybrid inhibitor of histone chaperone ASF1, GLYCEROL, ... (5 entities in total)
• Functional Keywords: histone chaperone rational design peptidomimetics foldamers, chaperone
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 39728.33

Authors

Bakail, M.,Mbianda, J.,Perrin, E.M.,Guerois, R.,Legrand, P.,Traore, S.,Douat, C.,Guichard, G.,Ochsenbein, F. (deposition date: 2020-07-22, release date: 2021-06-09, Last modification date: 2024-07-10)

Primary citation

Mbianda, J.,Bakail, M.,Andre, C.,Moal, G.,Perrin, M.E.,Pinna, G.,Guerois, R.,Becher, F.,Legrand, P.,Traore, S.,Douat, C.,Guichard, G.,Ochsenbein, F.
Optimal anchoring of a foldamer inhibitor of ASF1 histone chaperone through backbone plasticity.
Sci Adv, 7:-, 2021

PubMed Abstract: Sequence-specific oligomers with predictable folding patterns, i.e., foldamers, provide new opportunities to mimic α-helical peptides and design inhibitors of protein-protein interactions. One major hurdle of this strategy is to retain the correct orientation of key side chains involved in protein surface recognition. Here, we show that the structural plasticity of a foldamer backbone may notably contribute to the required spatial adjustment for optimal interaction with the protein surface. By using oligoureas as α helix mimics, we designed a foldamer/peptide hybrid inhibitor of histone chaperone ASF1, a key regulator of chromatin dynamics. The crystal structure of its complex with ASF1 reveals a notable plasticity of the urea backbone, which adapts to the ASF1 surface to maintain the same binding interface. One additional benefit of generating ASF1 ligands with nonpeptide oligourea segments is the resistance to proteolysis in human plasma, which was highly improved compared to the cognate α-helical peptide.

PubMed: 33741589
DOI: 10.1126/sciadv.abd9153

Experimental method

X-RAY DIFFRACTION (1.798 Å)