Crystal structures of two tropinone reductases: Different reaction stereospecificities in the same protein fold. (MOLECULAR BIOFUNCTION-Functional Molecular Conversion)

Abstract

A pair of tropinone reductases (TRs) share 64% identical amino acid residues, and belong to the shortchain dehydrogenase/reductase family. In the synthesis of tropane alkaloids in several medicinal plants, the TRs reduce a carbonyl group of an alkaloid intermediate, tropinone, to hydroxy groups having different diastereomeric configurations. To clarify the structural basis for their different reaction stereospecificities, we determined the crystal structures of the two enzymes at 2.4- and 2.3-A resolutions. The overall folding of the two enzymes was almost identical. The substrate binding site was composed mostly of hydrophobic amino acids in both TRs, but the presence of different charged residues conferred different electrostatic environments on the two enzymes.