The X-ray crystal structure of the membrane protein prostaglandin H2 synthase-1

Nature. 1994 Jan 20;367(6460):243-9. doi: 10.1038/367243a0.


The three-dimensional structure of prostaglandin H2 synthase-1, an integral membrane protein, has been determined at 3.5 A resolution by X-ray crystallography. This bifunctional enzyme comprises three independent folding units: an epidermal growth factor domain, a membrane-binding motif and an enzymatic domain. Two adjacent but spatially distinct active sites were found for its haem-dependent peroxidase and cyclooxygenase activities. The cyclooxygenase active site is created by a long, hydrophobic channel that is the site of non-steroidal anti-inflammatory drug binding. The conformation of the membrane-binding motif strongly suggests that the enzyme integrates into only one leaflet of the lipid bilayer and is thus a monotopic membrane protein.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Computer Graphics
  • Crystallography, X-Ray
  • Epidermal Growth Factor / chemistry
  • Flurbiprofen / chemistry
  • Isoenzymes / chemistry*
  • Isoenzymes / metabolism
  • Lipid Bilayers / metabolism
  • Membrane Proteins / chemistry*
  • Models, Molecular
  • Molecular Sequence Data
  • Peroxidases / chemistry
  • Peroxidases / metabolism
  • Prostaglandin-Endoperoxide Synthases / chemistry*
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Protein Conformation
  • Sheep


  • Isoenzymes
  • Lipid Bilayers
  • Membrane Proteins
  • Flurbiprofen
  • Epidermal Growth Factor
  • Peroxidases
  • Prostaglandin-Endoperoxide Synthases