Structure of the Imine Reductase from Ajellomyces dermatitidis in Three Crystal Forms

The NADPH-Dependent Imine Reductase from Ajellomyces dermatitidis (AdRedAm) catalyzes the reductive amination of certain ketones with amine donors, supplied in an equimolar ratio. We have determined the structure of AdRedAm in three forms. The first, in space group P3121, refined to 2.01 Å resolution, features two molecules (one dimer) in the asymmetric unit (asu), in complex with the redox inactive cofactor NADPH4. The second, in space group C21 and refined to 1.73 Å, has nine molecules (four and a half dimers) in the asu, each with NADP+. The third, space group P3121 and refined to 1.52 Å, had one molecule (one half-dimer) in the asu. The third structure was again in complex with NADP+ but also with the substrate 2,2-difluoroacetophenone. The different datasets permit analysis of AdRedAm in different conformational states and also reveal the molecular basis of stereoselectivity in the transformation of fluorinated acetophenone substrates by the enzyme.