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

D Picot, PJ Loll, RM Garavito - Nature, 1994 - nature.com
Nature, 1994nature.com
The three-dimensional structure of prostaglandin H2 synthase-1, an integral membrane
protein, has been determined at 3.5 Å 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 …
Abstract
The three-dimensional structure of prostaglandin H2 synthase-1, an integral membrane protein, has been determined at 3.5 Å 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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