The X-ray crystal structure of the membrane protein prostaglandin H2 synthase-1.
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.
Picot
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Department of Biochemistry and Molecular Biology, University of Chicago, Illinois 60637.
Loll
P J
PJ
Garavito
R M
RM
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003196:Computer Graphics; D018360:Crystallography, X-Ray; D004815:Epidermal Growth Factor / Q000737:chemistry; D005480:Flurbiprofen / Q000737:chemistry; D007527:Isoenzymes / Q000737:chemistry* / Q000378:metabolism; D008051:Lipid Bilayers / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010544:Peroxidases / Q000737:chemistry / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D012756:Sheep
D007527:Isoenzymes; D008051:Lipid Bilayers; D008565:Membrane Proteins; D005480:Flurbiprofen; D004815:Epidermal Growth Factor; D010544:Peroxidases; D011451:Prostaglandin-Endoperoxide Synthases