Modelling the amino acid sequence of NAD+-linked 15-hydroxyprostaglandin dehydrogenase into the three-dimensional structure of 3α/20β-hydroxysteroid dehydrogenase shows that these two enzymes, as well as the NADP+-linked prostaglandin dehydrogenase (identical to carbonyl reductase) have similar conformations, in spite of very limited sequence identity (23–28%). Conservation of tertiary structures is greatest over the first two thirds of the polypeptide chains, where the typical NAD+ binding fold is retained, including the five first β-strands, with only two short deletions or insertions up to residue 147. The remaining thirds of each of the prostaglandin dehydrogenases have significantly different architecture, including insertions that may contribute to enzyme specificity, and, except for an additional helix (αG), are difficult to model. Active site relationships can be evaluated and subunit interactions predicted, suggesting that the αE + αF two-helix surface constitutes the major subunit interacting area, forming a dimeric unit in the oligomeric enzymes.
