Multidrug resistance regulators (MDRs) as scaffolds for the design of artificial metalloenzymes.
The choice of protein scaffolds is an important element in the design of artificial metalloenzymes. Herein, we introduce Multidrug Resistance Regulators (MDRs) from the TetR family as a viable class of protein scaffolds for artificial metalloenzyme design. In vivo incorporation of the metal binding amino acid (2,2-bipyridin-5yl)alanine (BpyA) by stop codon suppression methods was used to create artificial metalloenzymes from three members of the TetR family of MDRs: QacR, CgmR and RamR. Excellent results were achieved with QacR Y123BpyA in the Cu2+catalyzed enantioselective vinylogous Friedel-Crafts alkylation reaction with ee's up to 94% of the opposite enantiomer that was achieved with other mutants and the previously reported LmrR-based artificial metalloenzymes.
Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands. j.g.roelfes@rug.nl.
Manuela
M
Bersellini
Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands. j.g.roelfes@rug.nl.
Gerard
http://orcid.org/0000-0002-0364-9564
G
Roelfes
D001426:Bacterial Proteins / Q000737:chemistry*; D040761:Biomimetic Materials / Q000737:chemistry*; D002384:Catalysis; D003300:Copper / Q000737:chemistry; D015195:Drug Design; D057927:Hydrophobic and Hydrophilic Interactions; D008667:Metalloproteins / Q000737:chemistry*; D008958:Models, Molecular; D011487:Protein Conformation
D001426:Bacterial Proteins; D008667:Metalloproteins; D003300:Copper