(predominantly by F) strongly correlates with the lack of the membrane-associated domain. The hydrophobic residues that interact with the substrate (A52, F338, A539) are usually substituted by other residues with similar biochemical properties (G52, L338, and P538 in 86%, 55% and 52% sequences, respectively). Our modelling confirmed the structure-based hypothesis that both Y536 and the main chain of G540 are involved in the directional binding of 3-ketosteroids.