Structural highlights
Function
1433S_HUMAN Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway (By similarity). p53-regulated inhibitor of G2/M progression.
Publication Abstract from PubMed
Rational design of protein-protein interaction (PPI) inhibitors is challenging. Connecting a general supramolecular protein binder with a specific peptidic ligand provides a novel conceptual approach. Thus, lysine-specific molecular tweezers were conjugated to a peptide-based 14-3-3 ligand and produced a strong PPI inhibitor with 100-fold elevated protein affinity. X-ray crystal structure elucidation of this supramolecular directed assembly provides unique molecular insight into the binding mode and fully aligns with Molecular Dynamics (MD) simulations. This new supramolecular chemical biology concept opens the path to novel chemical tools for studying PPIs.
Supramolecular Enhancement of a Natural 14-3-3 Protein Ligand.,Guillory X, Hadrovic I, de Vink PJ, Sowislok A, Brunsveld L, Schrader T, Ottmann C J Am Chem Soc. 2021 Sep 1;143(34):13495-13500. doi: 10.1021/jacs.1c07095. Epub , 2021 Aug 24. PMID:34427424[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Guillory X, Hadrović I, de Vink PJ, Sowislok A, Brunsveld L, Schrader T, Ottmann C. Supramolecular Enhancement of a Natural 14-3-3 Protein Ligand. J Am Chem Soc. 2021 Sep 1;143(34):13495-13500. PMID:34427424 doi:10.1021/jacs.1c07095
