His126 Substitution Shifts Perakine Reductase Activity from Carbonyl Reduction to Ene Reduction

Perakine reductase (PR) is an aldo-keto reductase (AKR) carbonyl reductase. His126 is one of the AKR catalytic tetrads in PR. Substitution of His126 with any other amino acids except Gln switched PR to an ene reductase. Molecular simulation suggested that the substrate-binding pose and the properties of the 126 residue determined the chemoselectivity. Given the strict conservation of His126 in AKR superfamily carbonyl reductases, modification of the corresponding site is a feasible strategy to design AKR-derived novel ene reductases.