Three-dimensional model of NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase and relationships to the NADP(+)-dependent enzyme (carbonyl reductase)

FEBS Lett. 1993 May 10;322(2):139-42. doi: 10.1016/0014-5793(93)81554-d.


Modelling the amino acid sequence of NAD(+)-linked 15-hydroxyprostaglandin dehydrogenase into the three-dimensional structure of 3 alpha/20 beta-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 beta-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 (alpha G), are difficult to model. Active site relationships can be evaluated and subunit interactions predicted, suggesting that the alpha E + alpha F two-helix surface constitutes the major subunit interacting area, forming a dimeric unit in the oligomeric enzymes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Computer Graphics
  • Humans
  • Hydroxyprostaglandin Dehydrogenases / chemistry*
  • Hydroxysteroid Dehydrogenases / chemistry*
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Sequence Homology, Amino Acid


  • Hydroxysteroid Dehydrogenases
  • Hydroxyprostaglandin Dehydrogenases
  • 15-hydroxyprostaglandin dehydrogenase