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Publication Abstract from PubMed

Supramolecular chemistry has recently emerged as a promising way to modulate protein functions, but devising molecules that will interact with a protein in the desired manner is difficult as many competing interactions exist in a biological environment (with solvents, salts or different sites for the target biomolecule). We now show that lysine-specific molecular tweezers bind to a 14-3-3 adapter protein and modulate its interaction with partner proteins. The tweezers inhibit binding between the 14-3-3 protein and two partner proteins-a phosphorylated (C-Raf) protein and an unphosphorylated one (ExoS)-in a concentration-dependent manner. Protein crystallography shows that this effect arises from the binding of the tweezers to a single surface-exposed lysine (Lys214) of the 14-3-3 protein in the proximity of its central channel, which normally binds the partner proteins. A combination of structural analysis and computer simulations provides rules for the tweezers' binding preferences, thus allowing us to predict their influence on this type of protein-protein interactions.

Molecular tweezers modulate 14-3-3 protein-protein interactions.,Bier D, Rose R, Bravo-Rodriguez K, Bartel M, Ramirez-Anguita JM, Dutt S, Wilch C, Klarner FG, Sanchez-Garcia E, Schrader T, Ottmann C Nat Chem. 2013 Mar;5(3):234-9. doi: 10.1038/nchem.1570. Epub 2013 Feb 17. PMID:23422566^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.