3-DIMENSIONAL MODEL OF NAD-DEPENDENT 15-HYDROXYPROSTAGLANDIN DEHYDROGENASE AND RELATIONSHIPS TO THE NADP+-DEPENDENT ENZYME (CARBONYL REDUCTASE)()

Modelling the amino acid sequence of NAD+-linked 15-hydroxyprostagland in dehydrogenase into the three-dimensional structure of 3alpha/20beta -hydroxysteroid dehydrogenase shows that these two enzymes, as well as the NADP+-linked prostaglandin dehydrogenase (identical to carbonyl r eductase) have similar conformations, in spite of very limited sequenc e identity (23-28%). Conservation of tertiary structures is greatest o ver the first two thirds of the polypeptide chains, where the typical NAD+ binding fold is retained, including the five first beta-strands, with only two short deletions or insertions up to residue 147. The rem aining thirds of each of the prostaglandin dehydrogenases have signifi cantly different architecture, including insertions that may contribut e to enzyme specificity, and, except for an additional helix (alphaG), are difficult to model. Active site relationships can be evaluated an d subunit interactions predicted, suggesting that the alphaE + alphaF two-helix surface constitutes the major subunit interacting area, form ing a dimeric unit in the oligomeric enzymes.