Lipoxygenase Interactions

脂氧合酶相互作用

• 批准号: 6332981
• 负责人: BETTY J GAFFNEY
• 金额: $ 7.3万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-07-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6332981
• 关键词: X ray crystallography; bioenergetics; catalyst; chemical structure function; computer simulation; crystallization; electrical property; electron spin resonance spectroscopy; electron transport; gene mutation; intermolecular interaction; iron; isomerase; lipoxygenase; manganese; metal complex; model design /development; nitric oxide; physical model; plant proteins; protein purification; radiotracer; soybeans; statistics /biometry; structural biology; tyrosine

Description (applicant's description): Organizing principles in cell biology are emerging now that help elucidate many earlier reports of links between lipoxygenases and disease states. Because oxidation products of unsaturated lipids (lipoxygenase products and others) are short-lived signaling molecules that act locally (autocrine and paracrine mediators), experiments with isolated components (the enzymes and molecules with which they interact) are used to determine mechanisms of action. The experiments proposed focus on species with unpaired electrons related to lipoxygenase mechanisms and address how electrons redistribute in catalytic intermediates. EPR spectroscopy is the primary biophysical tool to be applied in these studies. High frequency EPR, at 94 GHz, will be employed in many experiments. Specific aims: 1) The electronic structure of nitric oxide in the complex with iron in lipoxygenase will be determined by EPR. The complex is a model of iron-ligand interactions in lipoxygenase. Methods include high frequency EPR of frozen solutions and crystals and, in collaboration, lower frequency pulsed EPR. (2) The roles of two different tyrosines in a protein with activity downstream of lipoxygenase action (allene oxide synthase) will be determined. (3) The electronic structure of different oxidation states of a manganese-containing lipoxygenase will be examined by high frequency EPR.

描述（申请人的描述）：细胞生物学的组织原理 现在正在新兴，有助于阐明许多早期的报告 脂氧酶和疾病状态。因为不饱和的氧化产物 脂质（脂氧合酶产物和其他）是短寿命的信号分子 该在本地起作用（自分泌和旁分泌介质），孤立的实验 组分（与之相互作用的酶和分子）用于 确定作用机理。这些实验提出了针对物种的重点 与脂氧合酶机制有关的未配对电子，并解决电子的方式 在催化中间体中重新分布。 EPR光谱是主要的 这些研究将应用的生物物理工具。高频EPR，在94 GHz， 将用于许多实验。 具体目的： 1）用铁中的铁中的一氧化氮的电子结构 脂氧合酶将由EPR确定。该复合物是铁配体的模型 脂氧合酶的相互作用。方法包括冷冻的高频EPR 解决方案和晶体，以及合作的较低频率脉冲EPR。 （2）两种不同酪氨酸在蛋白质中具有活性下游的作用 将确定脂氧合酶作用（Allene氧化物合酶）的。 （3）A的不同氧化状态的电子结构 含有锰的脂氧酶将通过高频EPR检查。