8UN8

Solution conformations of a 12-mer peptide bearing a natural N-hydrophobic triangle

Summary for 8UN8

• Entry DOI: 10.2210/pdb8un8/pdb
• NMR Information: BMRB: 31119
• Descriptor: ACE-LEU-ASP-ALA-ALA-LEU-LEU-ALA-ALA-ALA-LYS-ALA-TRP-NH2 peptide (1 entity in total)
• Functional Keywords: hydrophobic triangle, protein binding
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 1238.48

Authors

Mi, T.X.,Burgess, K. (deposition date: 2023-10-18, release date: 2024-06-05, Last modification date: 2024-11-13)

Primary citation

Mi, T.,Nguyen, D.,Gao, Z.,Burgess, K.
Bioinformatics leading to conveniently accessible, helix enforcing, bicyclic ASX motif mimics (BAMMs).
Nat Commun, 15:4217-4217, 2024

PubMed Abstract: Helix mimicry provides probes to perturb protein-protein interactions (PPIs). Helical conformations can be stabilized by joining side chains of non-terminal residues (stapling) or via capping fragments. Nature exclusively uses capping, but synthetic helical mimics are heavily biased towards stapling. This study comprises: (i) creation of a searchable database of unique helical N-caps (ASX motifs, a protein structural motif with two intramolecular hydrogen-bonds between aspartic acid/asparagine and following residues); (ii) testing trends observed in this database using linear peptides comprising only canonical L-amino acids; and, (iii) novel synthetic N-caps for helical interface mimicry. Here we show many natural ASX motifs comprise hydrophobic triangles, validate their effect in linear peptides, and further develop a biomimetic of them, Bicyclic ASX Motif Mimics (BAMMs). BAMMs are powerful helix inducing motifs. They are synthetically accessible, and potentially useful to a broad section of the community studying disruption of PPIs using secondary structure mimics.

PubMed: 38760359
DOI: 10.1038/s41467-024-48323-z

Experimental method

SOLUTION NMR