An Artificial Cofactor Catalyzing the Baylis‐Hillman Reaction with Designed Streptavidin as Protein Host**
| Autor: | Horst Lechner, Vincent Ragnar Emann, Birte Höcker, Matthias Breuning |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Streptavidin
biocatalysis Pyridines artificial cofactors Crystal structure Molecular Dynamics Simulation 010402 general chemistry 01 natural sciences Biochemistry Cofactor Catalysis chemistry.chemical_compound streptavidin Baylis–Hillman reaction protein design Molecular Biology Peptide sequence Density Functional Theory biology 010405 organic chemistry Communication Organic Chemistry A protein Stereoisomerism Combinatorial chemistry Communications Transition state 0104 chemical sciences chemistry Mutagenesis Site-Directed biology.protein Molecular Medicine Baylis-Hillman reaction |
| Zdroj: | Chembiochem |
| ISSN: | 1439-7633 1439-4227 |
| Popis: | An artificial cofactor based on an organocatalyst embedded in a protein has been used to conduct the Baylis‐Hillman reaction in a buffered system. As protein host, we chose streptavidin, as it can be easily crystallized and thereby supports the design process. The protein host around the cofactor was rationally designed on the basis of high‐resolution crystal structures obtained after each variation of the amino acid sequence. Additionally, DFT‐calculated intermediates and transition states were used to rationalize the observed activity. Finally, repeated cycles of structure determination and redesign led to a system with an up to one order of magnitude increase in activity over the bare cofactor and to the most active proteinogenic catalyst for the Baylis‐Hillman reaction known today. A story in pictures: An artificial cofactor based on an organocatalyst was embedded in streptavidin to catalyze the Baylis‐Hillman reaction. The following protein design process was described by solved crystal structures for every design step, and the outcome of the chemical reaction was represented by using DFT calculations and MD simulations. |
| Databáze: | OpenAIRE |
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