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- Title
Accelerating the Association of the Most Stable Protein-Ligand Complex by More than Two Orders of Magnitude.
- Authors
Giese, Christoph; Eras, Jonathan; Kern, Anne; Schärer, Martin A.; Capitani, Guido; Glockshuber, Rudi
- Abstract
The complex between the bacterial type 1 pilus subunit FimG and the peptide corresponding to the N-terminal extension (termed donor strand, Ds) of the partner subunit FimF (DsF) shows the strongest reported noncovalent molecular interaction, with a dissociation constant ( KD) of 1.5×10−20 m. However, the complex only exhibits a slow association rate of 330 m−1 s−1 that limits technical applications, such as its use in affinity purification. Herein, a structure-based approach was used to design pairs of FimGt (a FimG variant lacking its own N-terminal extension) and DsF variants with enhanced electrostatic surface complementarity. Association of the best mutant FimGt/DsF pairs was accelerated by more than two orders of magnitude, while the dissociation rates and 3D structures of the improved complexes remained essentially unperturbed. A KD value of 8.8×10−22 m was obtained for the best mutant complex, which is the lowest value reported to date for a protein/ligand complex.
- Subjects
PROTEIN-ligand interactions; MOLECULAR interactions; PROTEIN engineering; ELECTROSTATIC interaction; HYDROGEN bonding
- Publication
Angewandte Chemie, 2016, Vol 128, Issue 32, p9496
- ISSN
0044-8249
- Publication type
Article
- DOI
10.1002/ange.201603652