OXYGEN UTILIZING MEMBRANE HEME PROTEINS

膜血红素氧气利用计划项目的目标 蛋白质是前列腺素H合成酶的结构特征 (GHS)和细胞色素C氧化酶(CcOX)在化学物质的背景下 在催化过程中发生的变化，因为这些酶与它们的 底物和生物膜。PGHS催化了第一步 前列腺素的生物合成--前列腺素的形成 来自花生四烯酸的过氧化氢，两个分子02和两个 电子。CcOX是一种呼吸电子末端的血红素/铜氧化酶- 催化02的净四电子还原为两电子的转移链 H20分子伴随着四个质子的移位 线粒体内膜(或细菌质膜)。确实有 五个项目和四个核心。项目一：环氧合酶催化和 自杀失活(史密斯)将检查花生四烯酸与 PGHS的环氧合酶位点、自杀失活机制和 H20通道在PGHS中的作用。项目II：生物的结构生物学 PGH合成酶(Garavito)的过氧化作用将检查结构 PGHS中过氧化物酶的催化作用及其结构基础 针对PGHS-1和PGHS-2过氧化活性的差异。 项目III：PGH合成酶-1和-2中的单位膜锚(DeWitt) 将测试PGHS-1和PGHS-2与单个 通过四个疏水面的膜双层的小叶 连续的两亲性螺旋存在于氨基末端的三分之一 蛋白质。项目四：解决细胞色素c中的底物对接问题 细胞色素氧化酶和前列腺素H合成酶(Babcock)的光谱 旨在了解CcOX和PGHSs对氧和过氧化氢的激活 以及在还原过程中释放自由能的机制 这些底物中。核心A、行政(史密斯)、核心B：膜 蛋白质表达和纯化(DeWitt)，核心C：结晶和 X射线结晶学(Garavito)和D芯：EPR和共振拉曼 光谱学(McCracken)提供行政和技术支持 这些项目。

The goal of this Program Project entitled Oxygen Utilizing Membrane Heme Proteins is to characterize the structures of prostaglandin H synthases (GHSs) and cytochrome c oxidase (CcOX) in the context of the chemical changes that occur during catalysis as these enzymes interact with their substrates and with biological membranes. PGHS catalyzes the initial step in the biosynthesis of prostanoids--the formation of prostaglandin endoperoxide H2 from arachidonic acid, two molecules of 02 and two electrons. CcOX is a terminal heme/Cu oxidase of the respiratory electron- transfer chain which catalyzes a net four electron reduction of 02 to two H20 molecules with concomitant translocation of four protons across the mitochondrial inner membrane (or bacterial plasma membrane). There are five projects and four cores. Project I: Cyclooxygenase Catalysis and Suicide Inactivation (Smith) will examine the binding of arachidonate to the cyclooxygenase site of PGHS, the mechanism of suicide inactivation and the role of H20 channels in PGHS. Project II: Structural Biology of Peroxidation by PGH Synthases (Garavito) will examine the structural aspects of peroxidase catalysis in PGHSs and discern the structural basis for the differences in the peroxidative activities of PGHS-1 and -2. Project III: Monotopic Membrane Anchors in PGH Synthases-1 and -2 (DeWitt) will test the hypothesis that PGHS-1 and PGHS-2 associate with a single leaflet of the membrane bilayer through hydrophobic faces of four contiguous amphipathic helices present in the amino-terminal third of the proteins. Project IV: Substrate Docking in Cytochrome c resolved Spectroscopy of Cytochrome Oxidases and PGH Synthases (Babcock) is designed to understand oxygen and peroxide activation by CcOX and PGHSs and the mechanisms by which the free energy is released in the reduction of these substrates. Core A. Administration (Smith), Core B: Membrane Protein Expression and Purification (DeWitt), Core C: Crystallization and X-ray Crystallography (Garavito) and Core D: EPR and Resonance Raman Spectroscopy (McCracken) provide administrative and technical support for these projects.