THE STRUCTURE OF AN EICOSANOID BIOSYNTHETIC COMPLEX

类二十烷酸生物合成复合物的结构

• 批准号: 7954261
• 负责人: MARCIA E. NEWCOMER
• 金额: $ 0.02万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7954261
• 关键词: Anabolism; Arachidonic Acids; Binding; Chimeric Proteins; Complex; Computer Retrieval of Information on Scientific Projects Database; Eicosanoids; Funding; Grant; Institution; Lipoxygenase; Membrane; Pathway interactions; Reaction; Research; Research Personnel; Resources; Source; Structure; United States National Institutes of Health; allene oxide synthase; research study; structural biology; synchrotron radiation

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A naturally occurring 8R-lipoxygenase (8R-LOX) and allene oxide synthase fusion (AOS) protein from Plexaura homomalla catalyses successive steps in a biosynthetic pathway. The intermediate in the reaction, the 8R-hydroperoxy derivative of arachidonic acid, is both hydrophobic and labile. In order to understand how an assembly of catalytic activities impacts the transfer of the reaction intermediate, and thus the efficiency of biosynthesis, we will determine the structure of the lipoxygenase-allene oxide synthase complex. We have determined the crystal structures of the independently expressed domains, and have shown that they associate into a heterodimer. In addition we have shown that Ca2+ binding promotes membrane binding of the lipoxygenase domain. Experiments to elucidate conformational changes that occur (1) during the catalytic cycle and (2) upon Ca2+ binding are also proposed.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 来自 Plexaurahomalla 的天然存在的 8R-脂氧合酶 (8R-LOX) 和丙二烯氧化物合酶融合 (AOS) 蛋白催化生物合成途径中的连续步骤。该反应的中间体是花生四烯酸的 8R-氢过氧衍生物，既疏水又不稳定。 为了了解催化活性的组合如何影响反应中间体的转移，从而影响生物合成的效率，我们将确定脂氧合酶-丙二烯氧化物合酶复合物的结构。我们已经确定了独立表达结构域的晶体结构，并表明它们缔合成异二聚体。 此外，我们还发现 Ca2+ 结合促进脂氧合酶结构域的膜结合。还提出了阐明 (1) 催化循环期间和 (2) Ca2+ 结合时发生的构象变化的实验。