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: 7721909
• 负责人: MARCIA E. NEWCOMER
• 金额: $ 0.19万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7721909
• 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

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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 来自Plexaura Homamalla的天然存在的8R-脂氧合酶（8R-LOX）和Allene氧化物合酶融合（AOS）蛋白在生物合成途径中催化了连续的步骤。反应中的中间体是蛛网膜酸的8R-氢过氧衍生物，既疏水又不稳定。 为了了解催化活性的组装如何影响反应中间体的转移，因此如何影响生物合成的效率，我们将确定lipoxygogyganase-allene氧化物合酶复合物的结构。我们已经确定了独立表达的结构域的晶体结构，并表明它们与异二聚体相关。 此外，我们已经表明Ca2+结合促进了脂氧合酶结构域的膜结合。还提出了阐明催化周期中发生的构象变化的实验和CA2+结合时（2）的实验。