Fig. 6.

Substrate specificity in AKRs and SoGDH. (A) 3-α-HSD bound to testosterone, showing amino acids important for substrate binding. Leu61 and Phe128 are specific for AKRs that bind steroids. (B) Human ADR bound to the inhibitor tolrestat. Val61 and Trp128 are specific for AKRs that bind sugars. (C) The empty active site as observed in the SoGDH–NAD⁺ complex. Despite SoGDH having a sugar as its natural substrate, it presents a Tyr at position 61 and an Asp at 128. It also has differences in positions 59 (Ser) and 93 (Arg). Tyr185 appears to be specific for L-GDH, since galactose-binding proteins use an aromatic amino acid to orient the ligand to the active site. 3-α-HSD PDB code: 1AFS; ADR PDB code: 2FZD.