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Title
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The X-ray crystal structure of the membrane protein prostaglandin H2 synthase-1.
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Authors
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D.Picot,
P.J.Loll,
R.M.Garavito.
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Ref.
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Nature, 1994,
367,
243-249.
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PubMed id
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Abstract
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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.
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