Picot D, Loll P J, Garavito R M
Department of Biochemistry and Molecular Biology, University of Chicago, Illinois 60637.
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.
前列腺素H2合酶-1是一种整合膜蛋白，其三维结构已通过X射线晶体学以3.5埃的分辨率确定。这种双功能酶由三个独立的折叠单元组成：一个表皮生长因子结构域、一个膜结合基序和一个酶结构域。发现了两个相邻但在空间上不同的活性位点，分别用于其血红素依赖性过氧化物酶和环氧化酶活性。环氧化酶活性位点由一个长的疏水通道形成，该通道是非甾体抗炎药结合的部位。膜结合基序的构象强烈表明该酶仅整合到脂质双层的一个小叶中，因此是一种单一位点膜蛋白。
