Unexpected Catalytic Activity of the Regulatory Protein QacR
- Resource Type
- Authors
- Cora Gutiérrez de Souza; Manuela Bersellini; Gerard Roelfes; Lur Alonso-Cotchico
- Source
- Subject
- chemistry.chemical_classification
chemistry.chemical_compound
Residue (chemistry)
Enzyme
chemistry
Biocatalysis
Stereochemistry
Mutagenesis
Enantioselective synthesis
TetR
Protonation
Reactivity (chemistry)
- Language
Natural proteins often present binding or functional promiscuity. In biocatalysis, this promiscuity has been exploited for accessing new-to-nature reactions. Here, we report an unexpected catalytic reactivity for the regulatory protein QacR from the TetR family of multidrug resistance regulators. QacR is able to catalyze the enatioselective tandem Friedel-Crafts / enantioselective protonation reaction of indoles with alpha substituted conjugated enones with up to 40% yield and 83% ee. Mutagenesis and computational studies support the hypothesis that an acidic residue in the binding pocket of the protein is responsible for protonating the enolate intermediate.